Leuprolide and Norethindrone

Medically reviewed on August 12, 2018

Pronunciation

(loo PROE lide & nor eth IN drone)

Index Terms

• Leuprolide Acetate and Norethindrone Acetate
• Leuprolide/Norethindrone Acetate
• Norethindrone and Leuprolide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Combination:

Lupaneta Pack: 1-month kit: leuprolide acetate 3.75 mg depot suspension for injection (1) and norethindrone acetate 5 mg oral tablets (30), 3-month kit: leuprolide acetate 11.25 mg depot suspension for injection (1) and norethindrone acetate 5 mg oral tablets (90) [contains polysorbate 80]

Brand Names: U.S.

• Lupaneta Pack

Pharmacologic Category

• Gonadotropin Releasing Hormone Agonist
• Progestin

Pharmacology

Leuprolide administration inhibits the production of estrogen through negative feedback of pituitary gonadotropins. This in turn decreases endometrial implants and symptoms of endometriosis such as pain. Norethindrone is used to decrease adverse events observed with the hypoestrogenic state caused by leuprolide and possibly mitigate bone mineral density loss (Surrey, 2010).

Use: Labeled Indications

Endometriosis: Management of initial and recurrent painful symptoms of endometriosis

Contraindications

Hypersensitivity to leuprolide, gonadotropin-releasing hormone (GnRH), GnRH-agonist analogs, norethindrone acetate, or any component of the formulation; undiagnosed abnormal uterine bleeding; breast cancer or other hormone-dependent neoplasms (current or a history of); hepatic tumors or disease; thrombotic or thromboembolic disorder (current or history of); pregnancy (or planned pregnancy during therapy); breastfeeding

Dosing: Adult

Endometriosis: Females: Note: Treatment consists of an oral norethindrone tablet used in conjunction with an IM leuprolide injection. The initial therapy should be limited to 6 months duration; a single re-treatment of not more than 6 additional months may be administered if symptoms recur. Maximum total duration of therapy is 12 months.

1 month:

Injection: IM: Leuprolide 3.75 mg as a single dose administered by healthcare provider once every month for up to 6 doses (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)

Tablet: Oral: Norethindrone 5 mg once daily for up to 6 months (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)

3 month:

Injection: IM: Leuprolide 11.25 mg as a single dose administered by healthcare provider once every 3 months for up to 2 doses (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)

Tablet: Oral: Norethindrone 5 mg once daily for up to 6 months (maximum initial therapy: 6 months; maximum cumulative therapy: 12 months)

Dosing: Geriatric

Not for use in postmenopausal women

Dosing: Pediatric

Not for use prior to menarche

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied). Use is contraindicated with hepatic tumors or disease.

Reconstitution

Syringe: Prior to use, contents of prefilled syringe must be mixed. Do not use if the powder is clumping or caking, or if the diluent is not clear prior to mixing. Screw components of the syringe together and hold upright. Slowly push plunger to mix contents; while holding upright, shake gently until a uniform suspension forms. Do not use if the powder does not go into suspension.

Administration

IM: Leuprolide: Administer IM in the gluteal area, anterior thigh, or deltoid. Do not use if a blood vessel is accidently penetrated (will be able to see aspirated blood below the transparent luer lock).

Tablet: Norethindrone: Administer orally.

Dietary Considerations

In clinical trials, women were given supplemental elemental calcium 1000 mg/day.

Storage

Syringe: Prior to reconstitution, store at room temperature at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Following reconstitution, administer within 2 hours.

Tablets: Store at room temperature at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

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. Consider therapy modification

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. Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

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. Consider therapy modification

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. Consider therapy modification

Barbiturates: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

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). Consider therapy modification

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. Consider therapy modification

Boceprevir: May increase the serum concentration of Progestins (Contraceptive). This has been seen specifically with drospirenone. Boceprevir may increase the serum concentration of Progestins (Contraceptive). This has been seen specifically with norethindrone. Management: Patients receiving boceprevir, ribavirin, and peginterferon alfa should use two reliable forms of contraception. Norethindrone/ethinyl estradiol may be used for one of these when norethindrone dose is at least 1 mg/day. Avoid drospirenone. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy

CarBAMazepine: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Carfilzomib: May enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification

Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Monitor therapy

CloBAZam: May decrease the serum concentration of Progestins (Contraceptive). Consider therapy modification

Cobicistat: May increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistat-containing products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. Consider therapy modification

Colesevelam: May decrease the serum concentration of Norethindrone. Consider therapy modification

Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

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). Consider therapy modification

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. Consider therapy modification

Darunavir: May decrease the serum concentration of Norethindrone. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Consider therapy modification

Encorafenib: May decrease the serum concentration of Progestins (Contraceptive). Avoid combination

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. Consider therapy modification

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. Consider therapy modification

Exenatide: May decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification

Felbamate: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Consider therapy modification

Flibanserin: Progestins (Contraceptive) may increase the serum concentration of Flibanserin. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

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. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

Griseofulvin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Avoid combination

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Monitor therapy

Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

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. Avoid combination

LamoTRIgine: May decrease the serum concentration of Progestins (Contraceptive). Monitor therapy

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. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

Macimorelin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Metreleptin: May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

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. Consider therapy modification

Mycophenolate: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Consider therapy modification

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. Consider therapy modification

Nevirapine: May decrease the serum concentration of Progestins (Contraceptive). Management: Instruct patients receiving nevirapine to use an alternative or additional nonhormonal contraceptive. Nevirapine product labeling however suggests that depo-medroxyprogesterone acetate may be used as a sole method of contraception. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

Pitolisant: May diminish the therapeutic effect of Progestins (Contraceptive). Management: The combination of hormonal contraceptives with pitolisant should be avoided, and an alternate means of contraception should be used. Consider therapy modification

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

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. Consider therapy modification

Primidone: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Prucalopride: May decrease the serum concentration of Progestins (Contraceptive). Consider therapy modification

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

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. Particularly, microdosed progesterone-only preparations may be inadequately effective. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Consider therapy modification

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. Consider therapy modification

Rufinamide: May decrease the serum concentration of Norethindrone. Consider therapy modification

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. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selegiline: Progestins (Contraceptive) may increase the serum concentration of Selegiline. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

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. Consider therapy modification

Telaprevir: May decrease the serum concentration of Progestins (Contraceptive). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Consider therapy modification

Thalidomide: Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Monitor therapy

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. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Consider therapy modification

Tranexamic Acid: Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination

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. Avoid combination

Vinflunine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

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. Consider therapy modification

Voriconazole: May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. Monitor therapy

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Test Interactions

See individual monographs.

Adverse Reactions

Percentages as reported with combination product. Also see individual agents.

>10%:

Central nervous system: Headache (46% to 51%), depression (27% to 34%), pain (21% to 29%), insomnia (13% to 15%), dizziness (7% to 11%), nervousness (4% to 11%)

Dermatologic: Dermatological reaction (9% to 11%)

Endocrine & metabolic: Hot flash (57% to 87%), decreased HDL cholesterol (41% to 44%), increased serum cholesterol (7% to 20%), androgen-like effect (5% to 18%), breast changes (8% to 13%), increased LDL cholesterol (7% to 11%)

Gastrointestinal: Nausea and vomiting (13% to 29%), change in bowel habits (constipation/diarrhea, 10% to 15%), weight gain (4% to 13%)

Genitourinary: Vaginitis (8% to 15%)

Neuromuscular & skeletal: Weakness (11% to 18%)

1% to 10%:

Cardiovascular: Edema (7% to 9%)

Central nervous system: Memory impairment (2% to 4%)

Endocrine & metabolic: Increased serum triglycerides (9% to 10%), decreased libido (4% to 7%), increased gamma-glutamyl transferase (1%)

Gastrointestinal: Dyspepsia (4% to 7%), change in appetite (6%)

Genitourinary: Irregular menses (≤5%)

Hepatic: Increased serum ALT (2%; ≥2 x ULN)

Local: Injection site reaction (3% to 9%)

Neuromuscular & skeletal: Leg cramps (3% to 9%)

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, asthma, nephrolithiasis, urinary tract infection

Warnings/Precautions

Concerns related to adverse effects:

• Allergic reactions: Anaphylactoid reactions and asthma exacerbations have been reported with therapy in patients with histories of asthma, sinusitis, or environmental or drug allergies.

• Decreased bone density: Leuprolide depot suspension may cause an irreversible loss in bone mineral density (BMD). Norethindrone reduces this loss; however, use of this combination should be limited in duration. The initial therapy should be limited to 6 months duration; a single re-treatment of not more than 6 additional months may be administered if symptoms recur. BMD should be measured prior to re-treatment. Maximum total duration of therapy is 12 months. Use caution in patients with additional risk factors for bone loss (eg, chronic alcohol or tobacco use, strong family history of osteoporosis, chronic use of medications that may decrease BMD such as corticosteroid therapy).

• Endometriosis: Due to the physiologic effects of the drug, exacerbation of endometriosis symptoms may occur after the first dose of leuprolide.

• Seizures: Convulsions have been observed with leuprolide in postmarketing reports; patients affected included both those with and without a history of cerebrovascular disorders, central nervous system anomalies or tumors, epilepsy, seizures, and those on concomitant medications which may lower the seizure threshold. If seizures occur, manage accordingly.

• Visual disturbances: Discontinue norethindrone pending examination if migraine, loss of vision, proptosis, diplopia, or other visual disturbances occur; discontinue this combination permanently if papilledema or retinal vascular lesions are observed on examination.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with risk factors for arterial disease or venous thromboembolism (VTE) (eg, hypertension, hypercholesterolemia, obesity, diabetes, family history of VTE, or women who smoke). Manage risk factors prior to therapy; monitor closely.

• Depression: Use with caution in patients with depression. Depression may occur or worsen during therapy; discontinue if serious depression recurs.

• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes, or cardiac or renal dysfunction.

Special populations:

• Elderly: Not for use in postmenopausal women.

• Pediatric patients: Not for use prior to menarche.

• Pregnancy: Pregnancy must be excluded prior to the start of treatment. Although leuprolide usually inhibits ovulation and stops menstruation, contraception is not ensured and a nonhormonal contraceptive should be used. Advise patients to notify their provider if they suspect or become pregnant.

Dosage form specific issues:

• Injection: Due to differing release characteristics, the 1-month and 3-month depot formulations of leuprolide are not equivalent and cannot be substituted for one another.

Monitoring Parameters

Pregnancy test (prior to therapy); bone mineral density (prior to re-treatment); endometrial-related pain; serum lipids

Pregnancy Risk Factor

X

Pregnancy Considerations

Use is contraindicated in females who are pregnant or who may become pregnant during therapy.

Pregnancy must be excluded prior to the start of treatment. Although leuprolide usually inhibits ovulation and stops menstruation, contraception is not ensured and a nonhormonal contraceptive should be used.

Fertility suppression observed with other leuprolide formulations is reversible following discontinuation of therapy. This formulation is indicated to treat pain associated with endometriosis; in infertile women with endometriosis, it does not necessarily improve the ability to conceive (ACOG 2010; ASRM 2012).

Also refer to individual monographs.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience acne, hot flashes, loss of strength and energy, insomnia, constipation, diarrhea, anxiety, or decreased libido. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), angina, tachycardia, severe behavioral changes, severe headache, severe nausea, severe vomiting, coughing up blood, severe dizziness, passing out, vision changes, blindness, bulging eyes, vaginitis, abnormal vaginal bleeding, urinary retention, painful urination, shortness of breath, excessive weight gain, swelling of arms or legs, breast pain, arrhythmia, sweating a lot, memory impairment, burning or numbness feeling, or bone pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling or face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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