LUPANETA PACK (leuprolide acetate for depot suspension and norethindrone acetate tablets) 1–Month 3.75 mg and 3–Month 11.25 mg are indicated for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms. The initial treatment course is limited to 6 months. If symptoms recur, a single treatment course of not more than 6 months may be administered. Use is not recommended longer than a total of 12 months due to concerns about adverse impact on bone mineral density.
Important Safety Information3
LUPANETA PACK 1–Month 3.75 mg and 3–Month 11.25 mg are contraindicated in:
- Patients who are hypersensitive to gonadotropin-releasing hormone (GnRH), GnRH agonist analogs or any of the excipients in leuprolide acetate for depot suspension, or norethindrone acetate
- Undiagnosed abnormal uterine bleeding
- Known, suspected, or planned pregnancy during the course of therapy
- Lactating women
- Known, suspected, or history of breast cancer or other hormone-sensitive cancer
- Current or history of thrombotic or thromboembolic disorder
- Liver tumors or liver disease
Leuprolide acetate for depot suspension induces a hypoestrogenic state resulting in loss of bone mineral density (BMD), some of which may not be reversible. In patients that are candidates for retreatment, it is recommended that bone density be assessed before retreatment. Retreatment with leuprolide acetate for depot suspension alone is not recommended.
In patients with major risk factors for loss of bone mineral content, risks and benefits of LUPANETA PACK must be weighed carefully before therapy is instituted, as use in this population may pose additional risks.
Leuprolide acetate may cause fetal harm if administered to a pregnant woman. Exclude pregnancy before initiating treatment with LUPANETA PACK. Use at the recommended dose usually inhibits ovulation and stops menstruation. Patients should use non-hormonal methods of contraception. Discontinue LUPANETA PACK if a patient becomes pregnant during treatment and inform the patient of potential risk to the fetus.
Discontinue norethindrone acetate tablets, pending examination, if there is a sudden partial or complete loss of vision or sudden onset of proptosis, diplopia, or migraine. Discontinue LUPANETA PACK if examination reveals papilledema or retinal vascular lesions.
Depression may occur or worsen during treatment with LUPANETA PACK. Carefully observe patients with a history of clinical depression and discontinue if the depression recurs to a serious degree.
In clinical trials of LUPANETA PACK, adverse events of asthma were reported in women with pre-existing histories of asthma, sinusitis, and environmental or drug allergies. Postmarketing reports of symptoms consistent with an anaphylactoid or asthmatic process have been reported.
Assess and manage risk factors for cardiovascular disease before starting LUPANETA PACK. Closely monitor women on norethindrone acetate who have risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (e.g., family history of VTE, obesity, and smoking).
An increase in clinical signs and symptoms may be observed during the initial days of therapy due to a temporary rise in sex steroids, but these should dissipate with continued therapy.
Norethindrone acetate may cause some degree of fluid retention; therefore, carefully observe women with conditions that might be influenced by this effect, such as epilepsy, migraines, or cardiac or renal dysfunctions.
Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy, including patients with and without concurrent medications and comorbid conditions.
Experience with LUPANETA PACK for treatment of endometriosis has been limited to women 18 years of age and older.
In controlled clinical trials, adverse events occurring in >10% of patients were hot flashes/sweats, headache/migraine, depression/emotional lability, nausea/vomiting, nervousness/anxiety, insomnia, pain, acne, asthenia, vaginitis, weight gain, constipation/diarrhea.
Uterine Leiomyomata (Fibroids)
LUPRON DEPOT® (leuprolide acetate for depot suspension)
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.
Advanced Prostate Cancer
LUPRON DEPOT 7.5 mg for 1–month, 22.5 mg for 3–month, 30 mg for
Central Precocious Puberty
LUPRON DEPOT-PED® (leuprolide acetate for depot suspension)
Important Safety Information1,2
General Information: LUPRON DEPOT, including
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
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
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
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.
Long-term androgen deprivation therapy (ADT) prolongs the QT interval. Consideration should be given to whether the benefits of ADT outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure, and in patients taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.
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 disorder, testicular atrophy, injection site reaction, joint disorders, asthenia, flu syndrome, skin reaction, 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
- 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.
References: 1. LUPRON DEPOT [package insert]. North Chicago, IL: AbbVie Inc.
2. LUPRON DEPOT-PED [package insert]. North Chicago, IL: AbbVie Inc.
3. LUPANETA PACK [package insert]. North Chicago, IL: AbbVie Inc.