Leuprorelin

Females treated for precocious puberty may experience menses or spotting during the first 2 months of treatment; notify health care provider if bleeding continues after the second month.

Androgen-deprivation therapy (ADT) may increase the risk for cardiovascular disease (Levine 2010). Sudden cardiac death and stroke have been reported in men receiving GnRH agonists. ADT may prolong the QT/QTc interval; consider the benefits of ADT versus the risk for QT prolongation in patients with a history of QTc prolongation, congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients with medications known to prolong the QT interval, or with preexisting cardiac disease. Consider periodic monitoring of electrocardiograms and electrolytes in at-risk patients.

Has been reported when used for ≥6 months. Use caution in patients with additional risk factors for bone loss (eg, chronic alcohol use, corticosteroid therapy).

Exacerbation of endometriosis or uterine leiomyomata may occur initially.

Diabetes and/or worsening of glycemic control have been reported in men receiving GnRH agonists. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) as clinically necessary.

Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with GnRH agonist administration (onset from 1 hour to usually • Psychiatric events: Psychiatric events have been described with GnRH agonists, including leuprolide; symptoms of emotional lability, irritability, impatience, anger, and aggression have been reported in postmarketing accounts. Monitor for development or worsening of psychiatric symptoms. Use with caution in patients with a history of psychiatric illness.

Convulsions have been observed in postmarketing reports in patients receiving GnRH agonists, including leuprolide; patients affected included both those with and without a history of cerebrovascular disorders, CNS anomalies or tumors, epilepsy, seizures, and those on concomitant medications which may lower the seizure threshold (eg, bupropion, SSRIs). If seizures occur, manage accordingly.

Has been reported when used for prostate cancer; closely observe patients for weakness and paresthesias in first few weeks of therapy. Observe patients with metastatic vertebral lesions closely.

Transient increases in testosterone (~50% above baseline) can lead to tumor flare, bone pain, hematuria, bladder outlet obstruction and neuropathy in prostate cancer patients during the first few weeks of therapy.

Has been reported when used for prostate cancer; closely observe patients for urinary tract obstruction and hematuria in first few weeks of therapy. Observe patients with urinary obstruction closely. Disease-related concerns:

Androgen deprivation therapy may increase the risk for cardiovascular disease, diabetes, insulin resistance, obesity, alterations in lipids, and fractures. Concomitant drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Vehicle used in injectable (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale). Due to different release properties, combinations of dosage forms or fractions of dosage forms should not be interchanged.

The Atrigel delivery system is a nongelatin-based, biodegradable, polymer matrix.

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Breast cancer: The American Society of Clinical Oncology (ASCO) Guideline Update on Ovarian Suppression for Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer (Burstein 2016) recommends that premenopausal women with higher-risk disease receive ovarian suppression (in addition to adjuvant endocrine therapy), although lower-risk patients should not; premenopausal women with stage II or stage III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should also receive ovarian suppression (in addition to endocrine therapy). Additionally, women with stage I or II breast cancers at higher risk of recurrence who might consider chemotherapy may be offered ovarian suppression (in addition to endocrine therapy). Women with stage 1 disease which does not require chemotherapy should receive endocrine therapy, but not ovarian suppression. Likewise, women with node-negative cancers 1 cm or less (T1a, T1b) should receive endocrine therapy, but not ovarian suppression. Guidelines from ASCO for Endocrine Therapy in Hormone Receptor-Positive Metastatic Breast Cancer (Rugo 2016) recommend that premenopausal women with ER-positive metastatic breast cancer start ovarian suppression, preferably in combination with hormonal therapy. While premenopausal patients without prior hormone therapy exposure can be treated with tamoxifen, or ovarian suppression, or ablation alone, combination therapy is preferred. In metastatic breast cancer, ovarian

Prostate cancer: Guidelines from the American Society of Clinical Oncology (ASCO) for hormonal management of advanced prostate cancer which is androgen-sensitive (Loblaw 2007) recommend either orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists as initial treatment for androgen deprivation.