Leuprolide and norethindrone (Lupaneta Pack) contain two medications that are used in the management of patients with painful episodes of endometriosis.
Leuprolide and norethindrone Uses:
-
Endometriosis:
- Leuprolide and norethindrone are used for the management of initial and recurrent painful symptoms of endometriosis.
Leuprolide and norethindrone (Lupaneta Pack) Dose in Adults:
Leuprolide and norethindrone (Lupaneta Pack) Dose in the treatment of Endometriosis:
- Females: Note: In the treatment of endometriosis the dose consists of an oral norethindrone tablet used in conjunction with an IM leuprolide injection.
- The first or initial therapy should be limited to six months duration.
- If the symptoms reappear an additional six or more months re-treatment may be administrated.
- The Maximum total duration of therapy is twelve months.
-
1 month:
- Injection: IM:
- Leuprolide 3.75 mg as a single dose administered by a healthcare provider once a month for up to 6 doses.
- The maximum initial therapy: 6 months;
- maximum cumulative therapy: 12 months
- Tablet: Oral: Norethindrone 5 mg one time a day for up to 6 months (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)
- Injection: IM:
-
3 month:
- Injection: IM:
- Leuprolide 11.25 mg as a single dose administered by healthcare provider one time in every 3 months for up to 2 doses.
- The maximum initial therapy: 6 months;
- The maximum cumulative therapy: 12 months.
- Tablet: Oral:
- Norethindrone 5 mg once daily for up to 6 months.
- The maximum initial therapy: 6 months;
- The maximum cumulative therapy: 12 months.
- Injection: IM:
Use in Children:
Not indicated.
Pregnancy Risk Factor X
- Females who are pregnant or have the potential to become pregnant while on therapy are not advised to use this medication.
- Before starting treatment, pregnant women must be excluded.
- Leuprolide can be used to stop menstruation and inhibit ovulation.
- Contraception is not guaranteed. A nonhormonal contraceptive should also be used during therapy.
- Other leuprolide formulations can cause fertility suppression. This is easily reversed once therapy is stopped.
- Although this formulation can be used to relieve the symptoms of endometriosis in women who are infertile, it will not improve your ability to conceive.
- For more information, see individual monographs.
Use of leuprolide or norethindrone during lactation
- It is unknown if breastmilk contains leuprolide. Breastmilk can contain small amounts of progestins.
- Breastfeeding women should avoid it.
Dose in Kidney Disease:
- No dosage adjustment is provided in the manufacturer's labeling as it has not been studied in patients with kidney disease.
Dose in Liver disease:
- No dosage adjustment is provided in the manufacturer's labeling as it has not been studied in patients with liver disease.
- It should be avoided in patients with liver diseases or hepatic malignancies.
- Percentages as reported with combination product.
Common Side Effects of Leuprolide and norethindrone (Lupaneta Pack):
-
Central Nervous System:
- Headache
- Depression
- Pain
- Insomnia
- Dizziness
- Nervousness
-
Dermatologic:
- Dermatological Reaction
-
Endocrine & Metabolic:
- Hot Flash
- Decreased HDL Cholesterol
- Increased Serum Cholesterol
- Androgen-Like Effect
- Breast Changes
- Increased LDL Cholesterol
-
Gastrointestinal:
- Nausea And Vomiting
- Change In Bowel Habits
- Weight Gain
-
Genitourinary:
- Vaginitis
-
Neuromuscular & Skeletal:
- Weakness
Less Common Side Effects of Leuprolide and norethindrone (Lupaneta Pack):
-
Cardiovascular:
- Edema
-
Central nervous system:
- Memory impairment
-
Endocrine & metabolic:
- Increased serum triglycerides
- Decreased libido
- Increased gamma-glutamyl transferase
-
Gastrointestinal:
- Dyspepsia
- Change in appetite
-
Genitourinary:
- Irregular menses
-
Hepatic:
- Increased serum ALT
-
Local:
- Injection site reaction
-
Neuromuscular & skeletal:
- Leg cramps
Contraindications to Leuprolide and norethindrone (Lupaneta Pack):
- Allergic reactions to leuprolide, Gonadotropin-releasing hormone (GnRH), GnRH-agonist analogs, norethindrone acetate, or any component of the formulation.
- Undiagnosed abnormal bleeding in the uterus
- Breast cancer, or any hormone-dependent cancer, may be present or past.
- Liver cancers and disease
- Patients who have a thrombotic disorder or thromboembolic disorder, whether they are current or past, should be evaluated.
- Individuals planning to get pregnant or going through pregnancy
- Breastfeeding
Warnings and precautions
-
Allergy reactions:
- Patients with allergies, asthma, sinusitis or environmental drug allergies have reported anaphylactic and allergic reactions.
- Patients may experience an increase in their asthma symptoms.
-
Reduced bone density
- The leuprolide depot suspension can cause irreversible bone mineral density loss.
- Norethindrone can reduce bone mineral density loss, but the combination therapy should be stopped for prolonged periods.
- The maximum duration of treatment should be six months. Recovery for six months may be possible if symptoms return.
- Before treatment re-initiation, monitor bone mineral density. The treatment should not last more than one year.
- Patients at high risk of bone loss should not take the drug. These are some risk factors for bone loss:
- Chronic alcohol and tobacco use
- Strong family history of osteoporosis
- Chronic use of medication that can reduce bone mineral density, such as corticosteroid treatment, may be detrimental.
-
Endometriosis:
- After the first dose, patients may experience an exacerbation in their symptoms.
-
Seizures:
- Seizures have been reported in patients.
- Patients at high risk for seizures should be warned about the dangers of taking this drug.
- These patients are at high risk include:
- Patients who have a history of cerebrovascular disorders
- Patients with CNS tumors and anatomic anomalies
- Patients who have had seizures or epilepsy in the past, as well as patients taking concomitant medication that lowers the seizure threshold.
-
Visual disturbances:
- Norethindrone should not be used by patients who have visual loss, proptosis or diplopia, as well as those suffering from migraine.
- If retinal vascular or papilledema are found, the treatment should be stopped immediately.
-
Cardiovascular disease
- Use with caution in patients with risk factors for arterial disease or venous thromboembolism (VTE) like hypertension, hypercholesterolemia, obesity, diabetes, family history of VTE, or women who smoke.
- Take control of risk factors and closely monitor patients.
-
Depression
- Patients with depression should be cautious
- Therapy may cause depression or make it worse. If you experience severe depression, the treatment should be stopped immediately.
-
Fluid retention can lead to more severe diseases
- Patients with fluid retention-related conditions such as asthma, epilepsy and migraine, cardiac dysfunction, cardiac or renal dysfunction, should be careful.
Leuprolide and norethindrone: Drug Interaction
|
Antidiabetic Agents |
Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. |
|
C1 inhibitors |
Progestins may enhance the thrombogenic effect of C1 inhibitors. |
|
Choline C 11 |
Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Elexacaftor |
Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor. Specifically, the risk for rash may be increased. |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Flibanserin |
Progestins (Contraceptive) may increase the serum concentration of Flibanserin. |
|
Haloperidol |
QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTcprolonging effect of Haloperidol. |
|
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca) |
May enhance the adverse/toxic effect of Progestins. |
|
LamoTRIgine |
May decrease the serum concentration of Progestins (Contraceptive). |
|
Metreleptin |
May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). |
|
QT-prolonging Agents (Highest Risk) |
QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Selegiline |
Progestins (Contraceptive) may increase the serum concentration of Selegiline. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Thalidomide |
Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Triazolam |
Hormonal Contraceptives may increase the serum concentration of Triazolam. |
|
Voriconazole |
May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. |
|
Risk Factor D (Consider therapy modification) |
|
|
Acitretin |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. |
|
Anticoagulants |
Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. |
|
Aprepitant |
May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. |
|
Artemether |
May decrease the serum concentration of Progestins (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. |
|
Atazanavir |
May increase the serum concentration of Progestins (Contraceptive). However, atazanavir may lead to decreased ethinyl estradiol concentrations and decreased effectiveness of oral contraceptive products. Management: Consider an alternative or additional method of contraception, particularly with combined estrogen/progestin products. Depot medroxyprogesterone acetate may be used without a need for additional contraception. |
|
Barbiturates |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. |
|
Bexarotene (Systemic) |
May decrease the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). |
|
Bile Acid Sequestrants |
May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. |
|
Bosentan |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. |
|
Brigatinib |
May decrease the serum concentration of Progestins (Contraceptive). Management: Females of childbearing potential should use an alternative, non-hormonal contraceptive during brigatinib therapy and for at least 4 months after the final brigatinib dose. |
|
CarBAMazepine |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. |
|
Carfilzomib |
May enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. |
|
Cenobamate |
May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use additional or alternative non-hormonal birth control while taking cenobamate. |
|
Cladribine |
May diminish the therapeutic effect of Hormonal Contraceptives. Management: Women using systemically acting hormonal contraceptives should add a barrier method during cladribine dosing and for at least 4 weeks after the last dose in each treatment course. |
|
CloBAZam |
May decrease the serum concentration of Progestins (Contraceptive). |
|
Cobicistat |
May increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistatcontaining products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. |
|
Colesevelam |
May decrease the serum concentration of Norethindrone. Management: Oral contraceptives containing ethinyl estradiol and norethindrone should be administered at least 4 hours before colesevelam. |
|
CYP3A4 Inducers (Strong) |
|
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Dabrafenib |
May decrease the serum concentration of Progestins (Contraceptive). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. |
|
Darunavir |
May decrease the serum concentration of Norethindrone. |
|
Efavirenz |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Eslicarbazepine |
May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. |
|
Exenatide |
May decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. |
|
Felbamate |
May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. |
|
Fosamprenavir |
Progestins (Contraceptive) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. |
|
Fosaprepitant |
May decrease the serum concentration of Progestins (Contraceptive). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. |
|
Fosphenytoin |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. |
|
Ivosidenib |
May decrease the serum concentration of Progestins (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. |
|
Lesinurad |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. |
|
Lixisenatide |
May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. |
|
Lopinavir |
May decrease the serum concentration of Progestins (Contraceptive). Lopinavir may increase the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate and etonogestrel implants may be used without a need for additional contraception. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
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Lumacaftor |
May decrease the serum concentration of Progestins (Contraceptive). Management: Do not rely on hormone-based contraceptives with concurrent use of lumacaftor/ivacaftor; an alternative, non-hormonal, method of contraception should be used if this combination is required. |
|
MiFEPRIStone |
May diminish the therapeutic effect of Progestins (Contraceptive). MiFEPRIStone may increase the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Mycophenolate |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. |
|
Nelfinavir |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. |
|
Oxcarbazepine |
May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. |
|
Perampanel |
May decrease the serum concentration of Progestins (Contraceptive). Management: Patients should use an alternative, nonhormonal-based form of contraception both during the concurrent use of perampanel and for 1 month after discontinuing perampanel. |
|
Phenytoin |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. |
|
Pitolisant |
May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. |
|
Pomalidomide |
Progestins may enhance the thrombogenic effect of Pomalidomide. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. |
|
Primidone |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. |
|
Retinoic Acid Derivatives |
May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Exceptions: Adapalene; Alitretinoin (Topical); Bexarotene (Topical); Tretinoin (Topical). |
|
Rifamycin Derivatives |
May decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. |
|
Rufinamide |
May decrease the serum concentration of Norethindrone. |
|
Saquinavir |
May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. |
|
St John's Wort |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. |
|
Sugammadex |
May decrease the serum concentration of Progestins (Contraceptive). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. |
|
Tetrahydrocannabinol and Cannabidiol |
May decrease the serum concentration of Hormonal Contraceptives. Management: Women using hormonal contraceptives should consider adding a barrier contraceptive due to the potential for tetrahydrocannabinol and cannabidiol to decrease concentrations and effectiveness of hormonal contraceptives. |
|
Tipranavir |
May increase the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. |
|
Topiramate |
May decrease the serum concentration of Progestins (Contraceptive). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. |
|
Vitamin K Antagonists (eg, warfarin) |
Progestins (Contraceptive) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. |
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Risk Factor X (Avoid combination) |
|
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Corifollitropin Alfa |
Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. |
|
Encorafenib |
May decrease the serum concentration of Progestins (Contraceptive). |
|
Griseofulvin |
May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. |
|
Indium 111 Capromab Pendetide |
Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. |
|
Ixazomib |
May decrease the serum concentration of Progestins (Contraceptive). More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of contraceptive progestins. Management: Patients of childbearing potential should use a nonhormonal barrier contraceptive during and 90 days following ixazomib treatment. |
|
Tranexamic Acid |
Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. |
|
Ulipristal |
Progestins may diminish the therapeutic effect of Ulipristal. Ulipristal may diminish the therapeutic effect of Progestins. Management: Ulipristal for uterine fibroids (Canadian indication): avoid progestins within 12 days of stopping ulipristal; as emergency contraceptive (U.S. indication): avoid progestins within 5 days of stopping ulipristal. |
Monitoring parameters:
- Perform a pregnancy test before treatment initiation.
- Perform a DEXA scan and monitor bone mineral density before re-treatment;
- Endometrial-related pain
- Serum lipids.
How to administer Leuprolide and norethindrone (Lupaneta Pack)?
- IM: Leuprolide:
- Administer the injection as deep IM injection in the gluteal area, anterior thigh, or deltoid muscles.
- Before injecting, pull the plunger, if blood is aspirated, do not administer the injection.
- Tablet: Norethindrone:
- Administer the tablet orally.
Mechanism of action of Leuprolide and norethindrone (Lupaneta Pack):
- Leuprolide administration decreases estrogen production through the negative feedback of pituitary gonotropins.
- This reduces the number of endometrial implants as well as symptoms such pain.
- Norethindrone can be used to reduce hypoestrogenic effects caused by leuprolide, and possibly to prevent bone mineral density loss.
- You can view individual monographs.
International Brand Names of Leuprolide and norethindrone:
- Lupaneta Pack
Leuprolide and norethindrone Brand Names in Pakistan:
- No Brands Available in Pakistan.
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