ADVERSE REACTIONS
The safety of ELIGARD® 7.5 mg was evaluated in eight surgically castrated males and 120 patients with advanced prostate cancer in two clinical trials. ELIGARD® 7.5 mg, like other LH-RH analogs, caused a transient increase in serum testosterone concentrations during the first week of treatment. Therefore, potential exacerbations of signs and symptoms of the disease during the first few 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).
In Study AGL9904, 120 patients were dosed with ELIGARD® 7.5 mg for up to six months and injection sites were closely monitored. In all, 716 injections of ELIGARD® 7.5 mg were administered. Transient burning/stinging was reported following 248 (34.6%) injections, with the majority (84%) of these events reported as mild. Pain was reported following 4.3% of study injections (18.3% of patients) and was generally reported as brief in duration and mild in intensity.
Erythema was reported following 2.6% of injections (12.5% of patients). These events were all reported as mild and generally resolved within a few days post-injection. Mild bruising was reported following 2.5% of injections (11.7% of patients). Pruritis, induration, and ulceration was reported following 1.4% (11 patients), 0.4% (3 patients), and 0.1% (1 patient) of study injections, respectively.
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 of up to six months of treatment with ELIGARD® 7.5 mg, and were reported in >/= 2% of patients (Tables 1 and 2). Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related are excluded.
Table 1: Incidence (%) of Possibly or Probably Related Systemic Adverse Events Reported by >/= 2% of Patients (n = 120) Treated with ELIGARD® 7.5 mg for up to Six Months in Study AGL9904
|
Body System
|
Adverse Event
|
Number
|
Percent
|
|
Body as a Whole
|
Malaise and Fatigue
|
21
|
17.5%
|
|
|
Dizziness
|
4
|
3.3%
|
|
Cardiovascular
|
Hot flashes/sweats *
|
68
|
56.7%
|
|
Genitourinary
|
Atrophy of Testes *
|
6
|
5.0%
|
|
Digestive
|
Gastroenteritis/Colitis
|
3
|
2.5%
|
|
Table 2: Incidence (%) of Possibly or Probably-Related Systemic Adverse Events Reported by >/= 2% of Surgically Castrated Patients (n = 8) Treated with a Single-Dose of ELIGARD® 7.5 mg in Study AGL9802
|
Body System
|
Adverse Event
|
Number
|
Percent
|
|
Cardiovascular
|
Hot flashes/sweats *
|
2
|
25.0%
|
|
In addition, the following possibly or probably related systemic adverse events were reported by < 2% of the patients using ELIGARD® 7.5 mg in clinical studies.
General: Sweating, insomnia, syncope
Gastrointestinal: Flatulence, constipation
Hematologic: Decreased red blood cell count, hematocrit and hemoglobin
Metabolic: Weight gain
Musculoskeletal: Tremor, backache, joint pain
Nervous: Disturbance of smell and taste, depression, vertigo
Skin: Alopecia
Urogenital: Testicular soreness, impotence *, decreased libido *, gynecomastia, breast soreness
*Expected pharmacological consequences of testosterone suppression. In the patient populations studied, a total of 86 hot flash/sweats adverse events were reported in 70 patients. Of these, 71 events (83%) were mild; 14 (16%) were moderate; 1 (1%) was severe.
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 an LH-RH agonist analog.3 It can be anticipated that long periods of medical castration in men will have effects on bone density.
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