Uterine Leiomyomata (Fibroids)
LUPRON DEPOT® (leuprolide acetate for depot suspension) 3.75 mg and 3-month 11.25 mg concomitantly with iron therapy are indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a 1-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. LUPRON DEPOT may be added if the response to iron alone is considered inadequate. Recommended duration of therapy with LUPRON DEPOT 3.75 mg is up to 3 months. The 3-month 11.25 mg dosage form is indicated only for women for whom 3 months of hormonal suppression is deemed necessary. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older.
LUPRON DEPOT 3.75 mg and 3-month 11.25 mg are indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions. LUPRON DEPOT with daily norethindrone acetate 5 mg is also indicated for initial management of endometriosis and for management of recurrence of symptoms. Duration of initial treatment or retreatment should be limited to 6 months.
Advanced Prostate Cancer
LUPRON DEPOT 7.5 mg for 1-month, 22.5 mg for 3-month, 30 mg for 4-month, and 45 mg for 6-month administration are indicated for the palliative treatment of advanced prostate cancer.
Central Precocious Puberty
LUPRON DEPOT-PED® (leuprolide acetate for depot suspension) 7.5 mg, 11.25 mg, and 15 mg for 1-month and 11.25 mg and 30 mg for 3-month administration are indicated in the treatment of children with central precocious puberty (CPP). CPP is defined as early onset of secondary sexual characteristics (generally earlier than 8 years of age in girls and 9 years of age in boys) associated with pubertal pituitary gonadotropin activation. It may show a significantly advanced bone age that can result in diminished adult height. Prior to initiation of treatment, confirm diagnosis of CPP by testing luteinizing hormone (LH) and sex steroid levels, and assess bone age versus chronological age. Baseline evaluations should be done to rule out intracranial tumor, steroid secreting tumors, a chorionic gonadotropin secreting tumor, and congenital adrenal hyperplasia.
Important Safety Information1,2
General Information: LUPRON DEPOT, including LUPRON DEPOT-PED, is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT; females who are or may become pregnant; women with undiagnosed abnormal vaginal bleeding; and women who are breastfeeding. LUPRON DEPOT may cause fetal harm when administered to pregnant women. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus, and that spontaneous abortion may occur. Before starting treatment with LUPRON DEPOT, pregnancy must be excluded. LUPRON DEPOT 7.5 mg for 1-month, 22.5 mg for 3-month, 30 mg for 4-month, and 45 mg for 6-month administration are not indicated for use in women. Transient worsening of symptoms or the occurrence of additional signs and symptoms may develop during the first few weeks of LUPRON DEPOT treatment in all indications. Due to the suppression of the pituitary-gonadal system by LUPRON DEPOT, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment, and for up to 6 months after discontinuation, may be affected. It usually inhibits ovulation and stops menstruation. Females should use non-hormonal methods of contraception. Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy, including patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications associated with convulsions, such as bupropion and SSRIs. Convulsions have also been reported in the absence of any of the conditions mentioned above. LUPRON DEPOT must be administered under the supervision of a physician.
Uterine Leiomyomata (Fibroids): Patients who have a history of depression should be carefully observed and counseled on the possibility of the development or worsening of depression and the occurrence of memory disorders. Mean changes in cholesterol, LDL, HDL, and the LDL/HDL ratios were observed. Induced hypoestrogenic state resulted in bone loss (average of 2.7% compared with the pretreatment value) over a course of treatment, which may not be reversible. In patients with major risk factors for decreased bone mineral content, LUPRON DEPOT therapy may pose an additional risk. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older. In controlled clinical trials of fibroid patients, adverse events occurring in >10% of patients were headache, vasomotor flushes, depression/emotional lability, and vaginitis.
Endometriosis: Patients who have a history of depression should be carefully observed and counseled on the possibility of the development or worsening of depression and the occurrence of memory disorders. Mean changes in cholesterol, LDL, HDL, and the LDL/HDL ratios were observed. Induced hypoestrogenic state resulted in bone loss (average of 3.2% compared with the pretreatment value) over a course of treatment, which may not be reversible. LUPRON DEPOT therapy alone may pose an additional risk in patients with major risk factors for bone loss. In these patients, concomitant treatment with daily norethindrone acetate 5 mg should be considered and retreatment beyond an initial 6-month course is not advisable. In patients who are candidates for retreatment with LUPRON DEPOT, bone density should be assessed before retreatment and concomitant treatment with norethindrone acetate is recommended. LUPRON DEPOT plus norethindrone acetate-treated patients had significantly decreased HDL levels and significantly increased LDL/HDL ratios in clinical trials. After discontinuation of treatment, mean serum lipid levels in clinical trial patients with follow-up data returned to pretreatment values. Experience with LUPRON DEPOT for treatment of endometriosis has been limited to women 18 years of age and older.
Hormonal add-back therapy: Norethindrone acetate is contraindicated in women with a history of thrombophlebitis, thromboembolic disorders, cerebral apoplexy, markedly impaired liver function or liver disease, or known or suspected carcinoma of the breast. Assessment and management of risk factors for cardiovascular disease is recommended prior to initiation of add-back therapy with norethindrone acetate and should be used with caution in women with risk factors, including lipid abnormalities or cigarette smoking. LUPRON DEPOT plus norethindrone acetate treatment should be discontinued if there is a sudden partial or complete loss of vision; if there is sudden onset of proptosis, diplopia, or migraine; or if examination reveals papilledema or retinal vascular lesions. In controlled clinical trials of endometriosis patients, with or without add-back therapy with norethindrone acetate, adverse events occurring in >20% of patients were headache, vasomotor flushes, depression/emotional lability, vaginitis, pain, nausea/vomiting, and insomnia/sleep disorder.
Advanced Prostate Cancer: LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause transient worsening of symptoms or additional signs and symptoms of prostate cancer; temporary increase in bone pain in a small number of patients, which can be managed symptomatically; isolated cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications. Observe patients with vertebral metastasis and/or urinary tract obstruction closely.
Periodic monitoring of serum testosterone and PSA levels is recommended.
Hyperglycemia and increased risk of developing diabetes have been reported in men receiving GnRH agonists. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in men receiving a GnRH agonist and manage hyperglycemia or diabetes.
An increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of GnRH agonists in men, although the risk appears low. Evaluate the risks carefully, including cardiovascular risk factors, when determining prostate cancer treatment. Men receiving a GnRH agonist should be monitored for signs and symptoms of cardiovascular disease and managed appropriately.
Androgen deprivation therapy (ADT) may prolong the QT/QTc interval. Consideration should be given to whether the benefits of ADT outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Correct electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes.
In controlled clinical trials of advanced prostatic cancer patients receiving any formulation of LUPRON DEPOT, the following adverse events occurred in >10% of patients: hot flashes/sweats, general pain, edema, urinary disorders, GI disorders, respiratory disorders, testicular atrophy, injection site reactions, joint disorders, asthenia, flu syndrome, skin reactions, headache, and fatigue/lethargy.
Central Precocious Puberty: Monitor adequate response initially and also with each dose change, or as judged clinically appropriate, with a GnRHa stimulation test, basal LH, or serum concentration of sex steroid levels:
- After 1-2 months of initiating therapy for 1-month formulations
- After 2-3 months of initiating therapy and at month 6 for 3-month formulations
- Measure for height and bone advancement every 6-12 months
Noncompliance with drug regimen or inadequate dosing may result in inadequate control of the pubertal process with gonadotropins and/or sex steroids increasing above prepubertal levels.
The most common adverse reactions with GnRH agonists, including LUPRON DEPOT-PED, are injection site reactions/pain including abscess and swelling, general pain, headache, emotional lability, hot flushes/sweating, acne/seborrhea, vaginitis/vaginal bleeding/vaginal discharge, rash including erythema multiforme, vasodilation, and increased weight.
LUPRON DEPOT-PED in children under 2 years of age is not recommended.