Lupaneta Pack

Last updated on RxList: 12/2/2020
Lupaneta Pack Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Lupaneta Pack?

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.

What Are Side Effects of Lupaneta Pack?

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.

Dosage for Lupaneta Pack

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.

What Drugs, Substances, or Supplements Interact with Lupaneta Pack?

Lupaneta Pack may interact with other drugs. Tell your doctor all medications and supplements you use.

Lupaneta Pack During Pregnancy and Breastfeeding

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.

Additional Information

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 Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, skin redness, severe itching; fast or pounding heartbeats; sweating, feeling like you might pass out; wheezing, difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical attention if you have signs of a pituitary gland problem: headache, vision problems, vomiting, changes in your mental status, severe weakness, cold or clammy skin, weak pulse, or feeling like you might pass out.

Call your doctor at once if you have:

  • sudden vision problems, sudden eye changes or discomfort;
  • sudden and severe headache;
  • mood changes, depression;
  • swelling, rapid weight gain;
  • ongoing symptoms of endometriosis;
  • a seizure;
  • chest pain or pressure, pain spreading to your jaw or shoulder;
  • liver problems--loss of appetite, stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes); or
  • signs of a blood clot--sudden numbness or weakness, problems with vision or speech, swelling or redness in an arm or leg, cough, wheezing, coughing up blood.

Common side effects may include:

  • headache;
  • weakness;
  • depressed mood;
  • minor vaginal bleeding or spotting, vaginal discharge or itching;
  • hot flashes, sweating;
  • nausea, vomiting, diarrhea, constipation;
  • feeling anxious or nervous;
  • sleep problems (insomnia);
  • weight gain; or
  • acne.

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.

Read the entire detailed patient monograph for Lupaneta Pack (Lupaneta Pack Leuprolide Acetate for Depot Suspension; Norethindrone Acetate Tablets)

SLIDESHOW

What Is Endometriosis? Symptoms, Causes, Treatment See Slideshow
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 ReactionsControlled StudyOpen Label Study
LA-Only*
N=51
LA/N†
N=55
LA/N†
N=136
N%N%N%
Any Adverse Reaction5098539612693
Body as a Whole
Asthenia181811
Headache/Migraine655146
Injection Site Reaction293
Pain242921
Cardiovascular System
Hot flashes/Sweats988757
Digestive System
Altered Bowel Function (constipation, diarrhea)141510
Changes in Appetite406
GI Disturbance (dyspepsia, flatulence)474
Nausea/Vomiting252913
Edema097
Weight Gain12134
Nervous System
Depression/Emotional Lability312734
Dizziness/Vertigo16117
Insomnia/Sleep Disorder311315
Decreased Libido1047
Memory Disorder624
Nervousness/Anxiety8411
Neuromuscular Disorder (leg cramps, paresthesia)293
Skin and Appendages
Androgen-Like Effects (acne, alopecia)4518
Skin/Mucous Membrane Reaction4911
Urogenital System
Breast Changes/Pain/Tenderness6138
Menstrual Disorders205
Vaginitis20158
* 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 VisitTreatment GroupNumber of Patients Reporting Hot FlashesNumber of Days with Hot FlashesMaximum Number of Hot Flashes in 24 Hours
N(%)N2MeanN2Mean
Week 24LA-Only*32/37863719365.8
LA/N†22/385813871381.91
* 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 mgleuprolide 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% ChangeBaseline Value*Wk 24% ChangeBaseline Value*Wk 24% Change
Total Cholesterol170.59.2%179.30.2%181.22.8%
HDL Cholesterol52.47.4%51.8-18.8%51.0-14.6%
LDL Cholesterol96.610.9%101.514.1%109.113.1%
LDL/HDL Ratio2.0†5.0%2.1†43.4%2.3†39.4%
Triglycerides107.817.5%130.29.5%105.413.8%
* 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

Controlled Study
(n=41)
Open Label Study
(n=117)
BaselineWk 24*BaselineWk 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:

  • Allergic reactions (anaphylactic, rash, urticaria, and photosensitivity reactions)
  • Mood swings, including depression
  • Suicidal ideation and attempt
  • Symptoms consistent with an anaphylactoid or asthmatic process
  • Localized reactions including induration and abscess at the site of injection
  • Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath), individually and collectively
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)

© 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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