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Included as part of the PRECAUTIONS section.

Tumor Flare

ELIGARD (leuprolide acetate) ® 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 (leuprolide acetate) ® 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.

Laboratory Tests

Response to ELIGARD (leuprolide acetate) ® should be monitored by measuring serum concentrations of testosterone and prostate specific antigen periodically.

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 (leuprolide acetate) ® 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 (leuprolide acetate) ® 22.5 mg.

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

Once castrate levels were achieved with ELIGARD (leuprolide acetate) ® 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 Diabetes

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.

Cardiovascular Diseases

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.

Nonclinical toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

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 (leuprolide acetate) ®.

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

Use In Specific Populations

Pregnancy

Pregnancy category X

[See ‘CONTRAINDICATIONS' section]

ELIGARD (leuprolide acetate) ® is contraindicated in women who are or may become pregnant while receiving the drug. Expected hormonal changes that occur with ELIGARD (leuprolide acetate) ® treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the potential risk for pregnancy loss.

In non-clinical studies in rats, 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 possibility exists that spontaneous abortion may occur.

Nursing Mothers

ELIGARD (leuprolide acetate) ® is not indicated for use in women [see INDICATIONS AND USAGE]. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ELIGARD (leuprolide acetate) ®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of ELIGARD (leuprolide acetate) ® in pediatric patients have not been established.

Geriatric Use

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

Last reviewed on RxList: 3/3/2011
This monograph has been modified to include the generic and brand name in many instances.