ADVERSE REACTIONS
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 Adverse Event
s
|
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 mild *
|
Pain (generally brief and mild) |
4.3% of injections (18.3% of patients) |
3.5% of injections (6.0% of patients) |
2.3% of injections † (3.3% of patients) |
4.6% of injections ‡
|
Erythema (generally brief and mild) |
2.6% of injections (12.5% of patients) |
0.9% of injections § (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 injections ¶
|
Pruritis |
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) |
|
|
|
* Following injection of ELIGARD® 30 mg, three of the 35 burning/stinging events were reported as moderate.
|
† 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.
|
‡ 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.
|
§ 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.
|
¶ 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 7). 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
®
|
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 |
Pruritis |
|
| 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.
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.
|
REPORTS OF SUSPECTED ELIGARD SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Eligard. The information is not vetted and should not be considered as verified clinical evidence.
Possible Eligard side effects / adverse reactions in 88 year old male
Reported by a consumer/non-health professional from Canada on 2011-10-13
Patient: 88 year old male
Reactions: Prostatic Specific Antigen Increased, Hot Flush, Testicular Disorder, Depression
Adverse event resulted in: disablity
Suspect drug(s):
Eligard
Dosage: frequency: every 3 months.
End date: 2011-10-01
Eligard
Dosage: frequency: every 3 months.
Start date: 2010-10-01
Other drugs received by patient: Ativan; Seroquel; Wellbutrin
Possible Eligard side effects / adverse reactions in 74 year old male
Reported by a physician from Czech Republic on 2011-10-31
Patient: 74 year old male weighing 110.0 kg (242.0 pounds)
Reactions: Pulmonary Embolism
Adverse event resulted in: hospitalization
Suspect drug(s):
Eligard
Indication: Prostate Cancer
Start date: 2010-05-27
End date: 2010-05-27
Casodex
Administration route: Oral
Indication: Prostate Cancer
Start date: 2010-05-27
End date: 2010-07-27
Eligard
Start date: 2011-07-19
End date: 2011-07-19
Other drugs received by patient: Antihypertensives
Possible Eligard side effects / adverse reactions in 79 year old male
Reported by a consumer/non-health professional from France on 2011-11-02
Patient: 79 year old male weighing 73.0 kg (160.6 pounds)
Reactions: Abdominal Pain, Chest Pain
Adverse event resulted in: hospitalization
Suspect drug(s):
Eligard
Other drugs received by patient: Acetaminophen and Tramadol HCL; Sotalol HCL; Diclofenac Sodium
|