INDICATIONS
Endometriosis
Monotherapy
LUPRON DEPOT® (leuprolide acetate for depot suspension) 3.75 mg or 11.25 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions.
In Combination with Norethindrone Acetate
LUPRON DEPOT 3.75 mg or 11.25 mg in combination with norethindrone acetate is indicated for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.
Use of norethindrone acetate in combination with LUPRON DEPOT 3.75 mg or 11.25 mg is referred to as add-back therapy and is intended to reduce the loss of bone mineral density (BMD) and reduce vasomotor symptoms associated with use of LUPRON DEPOT 3.75 mg or 11.25 mg.
Limitations of Use:
The total duration of therapy with LUPRON DEPOT 3.75 mg or 11.25 mg plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density.
Uterine Leiomyomata (Fibroids)
LUPRON DEPOT 3.75 mg or 11.25 mg used concomitantly with iron therapy is indicated for the preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary.
Consider a one-month trial period on iron alone, as some women will respond to iron alone. LUPRON DEPOT 3.75 mg or 11.25 mg may be added if the response to iron alone is considered inadequate.
Limitations of Use:
LUPRON DEPOT 3.75 mg or 11.25 mg is not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
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LUPRON DEPOT 3.75 mg or 11.25 mg is contraindicated in patients who are hypersensitive to gonadotropin-releasing hormone (GnRH), GnRH agonist analogs including leuprolide acetate, or any of the excipients in LUPRON DEPOT; in patients with undiagnosed abnormal uterine bleeding; and in pregnancy.
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When norethindrone acetate is administered with LUPRON DEPOT 3.75 mg or 11.25 mg, the contraindications to the use of norethindrone acetate also apply to this combination regimen. Refer to the norethindrone acetate prescribing information for a list of contraindications for norethindrone acetate.
WARNINGS AND PRECAUTIONS
Loss of Bone Mineral Density
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LUPRON DEPOT 3.75 mg or 11.25 mg induces a hypoestrogenic state that results in loss of bone mineral density (BMD), some of which may not be reversible after stopping treatment. In women with major risk factors for decreased BMD, such as chronic alcohol use (>3 units per day), tobacco use, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD, such as anticonvulsants or corticosteroids, use of LUPRON DEPOT may pose an additional risk. Carefully weigh the risks and benefits of LUPRON DEPOT use in these populations.
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The duration of LUPRON DEPOT 3.75 mg or 11.25 mg treatment is limited by the risk of loss of BMD.
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When using LUPRON DEPOT 3.75 mg or 11.25 mg for the management of endometriosis, combination use of norethindrone acetate (add-back therapy) is effective in reducing the loss of BMD that occurs with leuprolide acetate. Do not retreat with LUPRON DEPOT 3.75 mg or 11.25 mg without combination norethindrone acetate. Assess BMD before retreatment.
Embryo-Fetal Toxicity
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Based on animal reproduction studies and the drug’s mechanism of action, LUPRON DEPOT 3.75 mg or 11.25 mg may cause fetal harm if administered to a pregnant woman and is contraindicated in pregnant women. Exclude pregnancy prior to initiating treatment with LUPRON DEPOT 3.75 mg or 11.25 mg, if clinically indicated. Discontinue LUPRON DEPOT 3.75 mg or 11.25 mg if the woman becomes pregnant during treatment and inform the woman of potential risk to the fetus. Advise women to notify their healthcare provider if they believe they may be pregnant.
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When used at the recommended dose and dosing interval, LUPRON DEPOT 11.25 mg usually inhibits ovulation and stops menstruation. Contraception, however, is not ensured by taking LUPRON DEPOT 11.25 mg. If contraception is indicated, advise women to use non-hormonal methods of contraception while on treatment with LUPRON DEPOT 3.75 mg or 11.25 mg.
Hypersensitivity Reactions
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Acute hypersensitivity reactions, including anaphylaxis, have been reported with LUPRON DEPOT use. LUPRON DEPOT 3.75 mg or 11.25 mg is contraindicated in women with a history of hypersensitivity to gonadotropin-releasing hormone (GnRH) or GnRH agonist analogs.
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In clinical trials of LUPRON DEPOT 3.75 mg or 11.25 mg, adverse events of asthma were reported in women with pre-existing histories of asthma, sinusitis, and environmental or drug allergies. Symptoms consistent with an anaphylactoid or asthmatic process have been reported postmarketing.
- Delayed hypersensitivity reactions, including the severe cutaneous adverse reactions (SCAR) of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been rarely reported postmarketing in association with leuprolide-containing therapy. Discontinue future leuprolide therapy at first signs or symptoms of delayed hypersensitivity reactions.
Initial Flare of Symptoms
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Following the first dose of LUPRON DEPOT 3.75 mg or 11.25 mg, sex steroids temporarily rise above baseline because of the physiologic effect of the drug. Therefore, an increase in symptoms may be observed during the initial days of therapy, but these should dissipate with continued therapy.
Convulsions
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There have been postmarketing reports of convulsions in women on GnRH agonists, including leuprolide acetate. These included women with and without concurrent medications and comorbid conditions.
Clinical Depression
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Depression may occur or worsen during treatment with GnRH agonists, including LUPRON DEPOT 3.75 mg or 11.25 mg. Carefully observe women for depression, especially those with a history of depression, and consider whether the risks of continuing LUPRON DEPOT 3.75 mg or 11.25 mg outweigh the benefits. Women with new or worsening depression should be referred to a mental health professional, as appropriate.
Risks Associated with Norethindrone Combination Treatment
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If LUPRON DEPOT 3.75 mg or 11.25 mg is administered with norethindrone acetate, the warnings and precautions for norethindrone acetate apply to this regimen. Refer to the norethindrone acetate prescribing information for a full list of the warnings and precautions for norethindrone acetate.
ADVERSE REACTIONS
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Most common adverse reactions (>10%) in clinical trials were hot flashes/sweats, headache/migraine, vaginitis, depression/emotional lability, general pain, weight gain/loss, nausea/vomiting, decreased libido, and dizziness.
These are not all the possible side effects of LUPRON DEPOT 3.75 mg or 11.25 mg.
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Safety and effectiveness of LUPRON DEPOT 3.75 mg or 11.25 mg for management of endometriosis and the preoperative hematologic improvement of women with anemia caused by fibroids have been established in females of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. The safety and effectiveness of LUPRON DEPOT 3.75 mg or 11.25 mg for these indications have not been established in premenarcheal pediatric patients.
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LUPRON DEPOT 3.75 mg or 11.25 mg is not indicated in postmenopausal women and has not been studied in this population.
