Eligard (Leuprolide Acetate)

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 Events

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®

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.