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Lupaneta Pack

Last reviewed on RxList: 2/5/2016
Lupaneta Pack Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 2/5/2016

Lupaneta Pack (leuprolide acetate for depot suspension, norethindrone acetate tablets) contains a gonadotropin-releasing hormone (GnRH) agonist and a progestin, indicated for initial management of the painful symptoms of endometriosis, and management of recurrence of symptoms. Common side effects of Lupaneta Pack include hot flashes, sweats, headache, migraine, depression, mood swings, nausea, vomiting, nervousness, anxiety, sleep problems (insomnia), pain, acne, weakness, vaginal itching/discharge/pain (vaginitis), weight gain, constipation, diarrhea, breakthrough bleeding, and spotting.

The dose of Lupaneta Pack includes each component administered separately. Leuprolide acetate for depot suspension 3.75 mg is given by a healthcare provider as a single intramuscular injection every month for up to six injections (6 months of therapy). Norethindrone acetate 5 mg tablets are taken orally by the patient once per day for up to 6 months. Lupaneta Pack may interact with other drugs. Tell your doctor all medications and supplements you use. Lupaneta Pack is not recommended for use during pregnancy; it may harm a fetus. A doctor will administer a pregnancy test to rule out pregnancy before administering Lupaneta Pack. Non-hormonal methods of contraception are recommended while using Lupaneta Pack. It is unknown if the medications in Lupaneta Pack pass into breast milk, however, breastfeeding is not recommended.

Our Lupaneta Pack (leuprolide acetate for depot suspension, norethindrone acetate tablets) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Endometriosis occurs deep inside the uterus. See Answer
Lupaneta Pack Professional Information

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of co-administering leuprolide acetate for depot suspension and norethindrone acetate was evaluated in two clinical studies in which a total of 242 women were treated for up to one year. Women were treated with monthly IM injections of leuprolide acetate 3.75 mg (13 injections) alone or monthly IM injections of leuprolide acetate 3.75 mg (13 injections) and 5 mg norethindrone acetate daily. The population age range was 17-43 years old. The majority of patients were Caucasian (87%).

One study was a controlled clinical trial in which 106 women were randomized to one year of treatment with leuprolide acetate for depot suspension alone or with leuprolide acetate for depot suspension and norethindrone acetate. The other study was an open-label single arm clinical study in 136 women of one year of treatment with leuprolide acetate for depot suspension and norethindrone acetate, with follow-up for up to 12 months after completing treatment.

Adverse Reactions ( > 1%) Leading to Study Discontinuation

In the controlled study, 18% of patients treated monthly with leuprolide acetate and 18% of patients treated monthly with leuprolide acetate plus norethindrone acetate discontinued therapy due to adverse reactions, most commonly hot flashes (6%) and insomnia (4%) in the leuprolide acetate alone group and hot flashes and emotional lability (4% each) in the leuprolide acetate and norethindrone group.

In the open label study, 13% of patients treated monthly with leuprolide acetate plus norethindrone acetate discontinued therapy due to adverse reactions, most commonly depression (4%) and acne (2%).

Common Adverse Reactions

Table 1 lists the adverse reactions observed in at least 5% of patients in any treatment group, during the first 6 months of treatment in the add-back clinical studies, in which patients were treated with monthly leuprolide acetate for depot suspension 3.75 mg with or without norethindrone acetate co-treatment. The most frequently-occurring adverse reactions observed in these studies were hot flashes and headaches.

Table 1: Adverse Reactions Occurring in the First Six Months of Treatment in ≥ 5% of Patients with Endometriosis

Adverse Reactions Controlled Study Open Label Study
LA- Only*
N=51
LA/N†
N=55
LA/N†
N=136
N % N % N %
Any Adverse Reaction 50 98 53 96 126 93
Body as a Whole
  Asthenia   18   18   11
  Headache/Migraine   65   51   46
  Injection Site Reaction   2   9   3
  Pain   24   29   21
Cardiovascular System
  Hot flashes/Sweats   98   87   57
Digestive System
  Altered Bowel Function (constipation, diarrhea)   14   15   10
  Changes in Appetite   4   0   6
  GI Disturbance (dyspepsia, flatulence)   4   7   4
  Nausea/Vomiting   25   29   13
Metabolic and Nutritional Disorders
  Edema   0   9   7
  Weight Gain   12   13   4
Nervous System
  Depression/Emotional Lability   31   27   34
  Dizziness/Vertigo   16   11   7
  Insomnia/Sleep Disorder   31   13   15
  Decreased Libido   10   4   7
  Memory Disorder   6   2   4
  Nervousness/Anxiety   8   4   11
  Neuromuscular Disorder (leg cramps, paresthesia)   2   9   3
Skin and Appendages
  Androgen-Like Effects (acne, alopecia)   4   5   18
  Skin/Mucous Membrane Reaction   4   9   11
Urogenital System
  Breast Changes/Pain/Tenderness   6   13   8
  Menstrual Disorders   2   0   5
  Vaginitis   20   15   8
* LA-Only = leuprolide acetate 3.75 mg
† LA/N = leuprolide acetate 3.75 mg plus norethindrone acetate 5 mg

In the controlled clinical trial, 50 of 51 (98%) patients in the leuprolide acetate alone group and 48 of 55 (87%) patients in the leuprolide acetate and norethindrone group reported experiencing hot flashes on one or more occasions during treatment. Table 2 presents hot flash data in the sixth month of treatment.

Table 2: Hot Flashes in the Month Prior to the Assessment Visit (Controlled Study)

Assessment Visit Treatment Group Number of Patients Reporting Hot Flashes Number of Days with Hot Flashes Maximum Number of Hot Flashes in 24 Hours
N (%) N2 Mean N2 Mean
Week 24 LA-Only* 32/37 86 37 19 36 5.8
  LA/N† 22/38 581 38 71 38 1.91
* LA-Only = leuprolide acetate 3.75 mg
† LA/N = leuprolide acetate 3.75 mg plus norethindrone acetate 5 mg
1Statistically significantly less than the LA-Only group (p < 0.01)
2Number of patients assessed.

Serious Adverse Reactions

Urinary tract infection, renal calculus, depression

Changes in Laboratory Values during Treatment

Liver Enzymes

In the two clinical trials of women with endometriosis, 4 of 191 patients receiving leuprolide acetate and norethindrone acetate for up to 12 months developed an elevated (at least twice the upper limit of normal) SGPT and 2 of 136 developed an elevated GGT. Five of the 6 increases were observed beyond 6 months of treatment. None was associated with an elevated bilirubin concentration.

Lipids

Percent changes from baseline for serum lipids and percentages of patients with serum lipid values outside of the normal range in the two studies of leuprolide acetate and norethindrone acetate are summarized in the tables below. The major impact of adding norethindrone acetate to treatment with leuprolide acetate for depot suspension was a decrease in serum HDL cholesterol and an increase in the LDL/HDL ratio.

Table 3: Serum Lipids: Mean Percent Changes from Baseline Values at Treatment Week 24

  leuprolide acetate 3.75 mg leuprolide acetate for depot suspension 3.75 mg plus norethindrone acetate 5 mg daily
Controlled Study
(n=39)
Controlled Study
(n=41)
Open Label Study
(n=117)
Baseline Value* Wk 24% Change Baseline Value* Wk 24% Change Baseline Value* Wk 24% Change
Total Cholesterol 170.5 9.2% 179.3 0.2% 181.2 2.8%
HDL Cholesterol 52.4 7.4% 51.8 -18.8% 51.0 -14.6%
LDL Cholesterol 96.6 10.9% 101.5 14.1% 109.1 13.1%
LDL/HDL Ratio 2.0t 5.0% 2.11 43.4% 2.31 39.4%
Triglycerides 107.8 17.5% 130.2 9.5% 105.4 13.8%
* mg/dl
† ratio

Changes from baseline tended to be greater at Week 52. After treatment, mean serum lipid levels from patients with follow up data (105 of 158 patients) returned to pretreatment values.

Table 4: Percent of Patients with Serum Lipid Values Outside of the Normal Range

  leuprolide acetate for depot suspension 3.75 mg plus norethindrone acetate 5 mg daily
Controlled Study
(n=41)
Open Label Study
(n=117)
Baseline Wk 24* Baseline Wk 24*
Total Cholesterol ( > 240 mg/dL) 15% 20% 6% 7%
HDL Cholesterol ( < 40 mg/dL) 15% 44% 15% 41%
LDL Cholesterol ( > 160 mg/dL) 5% 7% 9% 11%
LDL/HDL Ratio ( > 4.0) 2% 15% 7% 21%
Triglycerides ( > 200 mg/dL) 12% 10% 5% 9%
* Includes all patients regardless of baseline value.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of leuprolide acetate for depot suspension or norethindrone acetate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Leuprolide Acetate for Depot Suspension

During postmarketing surveillance with other dosage forms and in the same or different populations, the following adverse reactions were reported:

Other adverse reactions reported are:

Hepato-biliary disorder - Serious liver injury

Injury, poisoning and procedural complications - Spinal fracture

Investigations - Decreased white blood count

Musculoskeletal and connective tissue disorder - Tenosynovitis-like symptoms

Nervous System disorder - Convulsion, peripheral neuropathy, paralysis

Vascular disorder - Hypotension, Hypertension

Serious venous and arterial thrombotic and thromboembolic events, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and transient ischemic attack

Pituitary Apoplexy

During post-marketing surveillance, cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of leuprolide acetate and other GnRH agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Read the entire FDA prescribing information for Lupaneta Pack (Lupaneta Pack Leuprolide Acetate for Depot Suspension; Norethindrone Acetate Tablets)

SLIDESHOW

What Is Endometriosis? Symptoms, Causes, Treatment See Slideshow
Related Resources for Lupaneta Pack

© Lupaneta Pack Patient Information is supplied by Cerner Multum, Inc. and Lupaneta Pack Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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