INDICATION1

Lo Loestrin Fe® is an estrogen/progestin combination oral contraceptive (COC) indicated for use by women to prevent pregnancy. The efficacy of Lo Loestrin Fe in women with a body mass index (BMI) of >35 kg/m2 has not been evaluated.

IMPORTANT SAFETY INFORMATION1

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke.

CONTRAINDICATIONS

Lo Loestrin Fe is contraindicated in women with a high risk of arterial or venous thrombotic diseases, liver tumors (benign or malignant) or liver disease, undiagnosed abnormal uterine bleeding, or breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past, and in women using Hepatitis C drugs containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

WARNINGS AND PRECAUTIONS

Discontinue Lo Loestrin Fe if a thrombotic event occurs, and at least 4 weeks before and through 2 weeks after major surgery. Lo Loestrin Fe should not be started any earlier than 4 weeks after delivery, in women who are not breastfeeding. If jaundice occurs, treatment should be discontinued.

Lo Loestrin Fe should not be prescribed for women with uncontrolled hypertension or hypertension with vascular disease. Women who are prediabetic or diabetic should be monitored while using Lo Loestrin Fe. Alternative contraceptive methods should be considered for women with uncontrolled dyslipidemia. Patients using Lo Loestrin Fe who have a significant change in headaches or irregular bleeding or amenorrhea should be evaluated. Lo Loestrin Fe should be discontinued during pregnancy.

ADVERSE REACTIONS

In the clinical trial for Lo Loestrin Fe, serious adverse reactions included deep vein thrombosis, ovarian vein thrombosis, and cholecystitis. The most common adverse reactions (incidence ≥2%) were nausea/vomiting, headache, bleeding irregularities, dysmenorrhea, weight fluctuation, breast tenderness, acne, abdominal pain, anxiety, and depression.

Patients should be counseled that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Please see full Prescribing Information,  including Boxed Warning for Lo Loestrin Fe.

INDICATION2

LILETTA® is a sterile, levonorgestrel-releasing intrauterine system indicated for prevention of pregnancy for up to 6 years. The system should be replaced after 6 years if continued use is desired.

IMPORTANT SAFETY INFORMATION2
Who is not appropriate for LILETTA

Use of LILETTA is contraindicated in women with the following: pregnancy; for use as post-coital contraception; congenital or acquired uterine anomaly, including fibroids, if they distort the uterine cavity and would be incompatible with correct IUS placement; known or suspected breast cancer or other hormone-sensitive cancer, now or in the past; known or suspected uterine or cervical neoplasia; acute liver disease or liver tumor; untreated acute cervicitis or vaginitis, including lower genital tract infections (eg, bacterial vaginosis) until infection is controlled; infected abortion in the past 3 months; unexplained uterine bleeding; a current IUS; acute pelvic inflammatory disease (PID) or endometritis or history of PID (except with later intrauterine pregnancy); conditions increasing susceptibility to pelvic infection; or hypersensitivity to any component of LILETTA.

Clinical considerations for use and removal of LILETTA

Use LILETTA with caution after careful assessment in patients with coagulopathy or taking anticoagulants; migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia; exceptionally severe or frequent headache; marked increase of blood pressure; or severe arterial disease such as stroke or myocardial infarction. Consider removing LILETTA if the following arise during use: uterine or cervical malignancy or jaundice. Because irregular bleeding/spotting is common during the first months of LILETTA use, exclude endometrial pathology (polyps or cancer) prior to the insertion of LILETTA in women with persistent or uncharacteristic bleeding. If the threads are not visible or are significantly shortened, they may have broken or retracted into the cervical canal or uterus. If LILETTA is displaced (eg, expelled or perforated the uterus), remove it.

Pregnancy-related risks with LILETTA

If pregnancy should occur with LILETTA in place, remove the intrauterine system because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal or manipulation may result in pregnancy loss. Evaluate women for ectopic pregnancy because the likelihood of a pregnancy being ectopic is increased with LILETTA. Tell women about the signs of ectopic pregnancy and associated risks, including loss of fertility. Women with a history of ectopic pregnancy, tubal surgery, or pelvic infection carry a higher risk of ectopic pregnancy.

Educate her about PID or endometritis

Insertion of LILETTA is contraindicated in the presence of known or suspected PID or endometritis or a history of PID unless there has been a subsequent intrauterine pregnancy. IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. One woman diagnosed with PID and two women diagnosed with endometritis developed the infection within a week of insertion. One endometritis case was diagnosed at 39 days after insertion. The remaining 11 cases of PID and endometritis were diagnosed more than 6 months after insertion, including one at 30 days after IUS removal. Counsel women who receive LILETTA to notify a healthcare provider if they develop lower abdominal or pelvic pain, fever, chills, unusual or malodorous discharge, unexplained bleeding, genital lesions or sores, or dyspareunia. PID and endometritis are often associated with sexually transmitted infections (STIs); LILETTA does not protect against STIs, including HIV. PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae. Inform women about the possibility of PID or endometritis and that these infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death.

Expect changes in bleeding patterns with LILETTA

Spotting and irregular or heavy bleeding may occur during the first 3 to 6 months. Periods may become shorter and/or lighter thereafter. Cycles may remain irregular, become infrequent, or even cease. Consider pregnancy if menstruation does not occur within 6 weeks of the onset of previous menstruation. If a significant change in bleeding develops during prolonged use, conduct diagnostic tests to assess possible endometrial pathology.

Be aware of other serious complications and most common adverse reactions

Some serious complications with IUSs like LILETTA are sepsis, perforation, and expulsion. Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of LNG-releasing IUSs. Aseptic technique during insertion of LILETTA is essential to minimize serious infections such as GAS.

Perforation (total or partial, including penetration/embedment of LILETTA in the uterine wall or cervix) may occur, most often during insertion, although the perforation may not be detected until sometime later. Perforation may also occur at any time during use. Perforation may reduce contraceptive efficacy. If perforation is suspected, locate and remove LILETTA as soon as possible. Surgery may be required. Delayed detection or removal of LILETTA in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera. The risk of perforation is higher if inserted in lactating women and may be higher if inserted in women who are postpartum or when the uterus is fixed retroverted.

Partial or complete expulsion of LILETTA may occur, resulting in the loss of contraceptive protection.

Delay LILETTA insertion a minimum of 4 weeks or until uterine involution is complete following a delivery or a second trimester abortion. Remove a partially expelled LILETTA. If expulsion has occurred, a new LILETTA may be inserted within 7 days after the onset of a menstrual period after pregnancy has been ruled out.

Ovarian cysts may occur and are generally asymptomatic, but may be accompanied by pelvic or abdominal pain or dyspareunia. Evaluate persistent ovarian cysts.

In the LILETTA clinical trial, the most common adverse reactions (≥5% users) were vulvovaginal mycotic infections (19.2%), vaginal bacterial infections (18.6%), acne (15.3%), nausea or vomiting (10.3%), abdominal discomfort or pain (9.9%), headache (9.5%), breast tenderness or pain (9.5%), dyspareunia (9.3%), anxiety (8.8%), pelvic discomfort or pain (8.4%), depression (8.3%), dysmenorrhea (6.4%), mood changes (6.3%), increased weight (5.9%), back pain (5.9%), and vaginal discharge (5.5%).

Teach patients to recognize and immediately report signs or symptoms of the aforementioned conditions. Evaluate patients 4 to 6 weeks after insertion of LILETTA and then yearly or more often if clinically indicated.

Please see full Prescribing Information 

INDICATION3

ORIAHNN® (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules) is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Use of ORIAHNN should be limited to 24 months due to the risk of continued bone loss, which may not be reversible.

IMPORTANT SAFETY INFORMATION3
THROMBOEMBOLIC AND VASCULAR EVENTS

Estrogen and progestin combinations, including ORIAHNN, increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at increased risk for these events. 

ORIAHNN is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke and women with uncontrolled hypertension. 

CONTRAINDICATIONS
  • ORIAHNN is contraindicated in women at a high risk of arterial, venous thrombotic, or thromboembolic disorders; who are pregnant; with known osteoporosis; current or history of breast cancer or other hormonally sensitive malignancies; known hepatic impairment or disease; undiagnosed abnormal uterine bleeding; known anaphylactic reaction, angioedema, or hypersensitivity to ingredients of ORIAHNN; or with concomitant use of organic anion transporting polypeptide (OATP) 1B1 inhibitors that are known or expected to significantly increase elagolix plasma concentrations.
    WARNINGS AND PRECAUTIONS
    Thromboembolic Disorders and Vascular Events
    • ORIAHNN is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events. Components of ORIAHNN increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at high risk for these events. In general, the risk is greatest among women over 35 years of age who smoke, and women with uncontrolled hypertension, dyslipidemia, vascular disease, or obesity.
    • Discontinue ORIAHNN if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs. If feasible, discontinue ORIAHNN at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Stop ORIAHNN if there is sudden, unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    Bone Loss
    • ORIAHNN is contraindicated in women with known osteoporosis. ORIAHNN may cause a decrease in bone mineral density (BMD) in some patients, which is greater with increasing duration of use and may not be completely reversible after stopping treatment.
    • The impact of ORIAHNN-associated decreases in BMD on long-term bone health and future fracture risk is unknown. Consider the benefits and risks of ORIAHNN in patients with a history of low-trauma fracture or other risk factors for osteoporosis or bone loss, including those taking medications that may decrease BMD (e.g., systemic or chronic inhaled corticosteroids, anticonvulsants, or proton pump inhibitors).
    • Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing ORIAHNN if the risk associated with bone loss exceeds the potential benefit of treatment. Limit the duration of use to 24 months to reduce the extent of bone loss.
    Hormonally Sensitive Malignancies
    • ORIAHNN is contraindicated in women with current or a history of breast cancer and in women at increased risk for hormonally sensitive malignancies, such as those with mutations in BRCA genes.
    • The use of estrogen alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. Surveillance measures, such as breast examinations and regular mammography, are recommended. Discontinue ORIAHNN if a hormonally sensitive malignancy is diagnosed.
    Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders
    • Depression, depressed mood, and/or tearfulness were reported at a higher incidence in women taking ORIAHNN (3%) compared with placebo (1%) in the Phase 3 clinical trials. Suicidal ideation and behavior, including a completed suicide, occurred in women treated with lower doses of elagolix in clinical trials conducted for a different indication.
    • Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits. Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate.
    • Advise patients to seek immediate medical attention for suicidal ideation and behavior. Reevaluate the benefits and risks of continuing ORIAHNN if such events occur.
    Hepatic Impairment and Transaminase Elevations
    • ORIAHNN is contraindicated in women with known hepatic impairment or disease.
    • Transaminase elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred with ORIAHNN in Phase 3 clinical trials. No pattern in time to onset of these liver transaminase elevations was identified. Transaminase levels returned to baseline within 4 months after peak values in these patients.
    • Instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury, such as jaundice.
    Elevated Blood Pressure
    • ORIAHNN is contraindicated in women with uncontrolled hypertension. Maximum mean increases in systolic blood pressure occurred at Month 5, and a mean maximum increase in diastolic blood pressure occurred at Month 4 in ORIAHNN-treated women, as compared to placebo-treated women.
    • For women with well-controlled hypertension, continue to monitor blood pressure and stop ORIAHNN if blood pressure rises significantly. Monitor blood pressure in normotensive women treated with ORIAHNN.
    Gallbladder Disease or History of Cholestatic Jaundice
    • Studies among estrogen users suggest a small increased relative risk of developing gallbladder disease. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, assess the risk-benefit of continuing therapy. Discontinue ORIAHNN if jaundice occurs.
    Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy
    • ORIAHNN may delay the ability to recognize the occurrence of a pregnancy because it may reduce the intensity, duration, and amount of menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue ORIAHNN if pregnancy is confirmed.
    • The effect of hormonal contraceptives on the efficacy of ORIAHNN is unknown. Advise women to use non-hormonal contraception during treatment and for 28 days after discontinuing ORIAHNN.
    Effects on Carbohydrate and Lipid Metabolism
    • ORIAHNN may decrease glucose tolerance and result in increased glucose levels. More frequent monitoring in ORIAHNN-treated women with prediabetes and diabetes may be needed.
    • In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Use of elagolix is associated with increases in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and serum triglycerides. Monitor lipid levels and consider discontinuing ORIAHNN if hypercholesterolemia or hypertriglyceridemia worsens.
    Alopecia
    • In Phase 3 clinical trials, more women experienced alopecia, hair loss, and hair thinning with ORIAHNN (3.5%) compared to placebo (1.0%). In almost one-third of affected ORIAHNN-treated women, alopecia was the reason for discontinuing treatment. No specific pattern was described. In the majority of these women, hair loss was continuing when ORIAHNN was stopped. Whether the hair loss is reversible is unknown. Consider discontinuing ORIAHNN if hair loss becomes a concern.
    Effect on Other Laboratory Results
    • The use of estrogen and progestin combinations may raise serum concentrations of binding proteins (e.g., thyroid-binding globulin, corticosteroid-binding globulin), which may reduce the free thyroid or corticosteroid hormone levels. Patients with hypothyroidism and hypoadrenalism may require higher doses of thyroid hormone or cortisol replacement therapy, respectively.
    • The use of estrogen and progestin may also affect the levels of sex hormone-binding globulin, coagulation factors, lipids, and glucose.
    RISK OF ALLERGIC REACTIONS DUE TO THE INACTIVE INGREDIENT (FD&C YELLOW NO. 5)
    • ORIAHNN contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
    ADVERSE REACTIONS
    • Most common adverse reactions occurring in ≥5% of women receiving ORIAHNN in clinical trials were hot flush, headache, fatigue, and metrorrhagia.

    These are not all of the possible side effects of ORIAHNN.

    Safety and effectiveness of ORIAHNN in pediatric patients have not been established.

    Please see Full Prescribing Information

    INDICATION4

    ORILISSA® (elagolix) is indicated for the management of moderate to severe pain associated with endometriosis. Limit the duration of use based on the dose and coexisting condition.

    IMPORTANT SAFETY INFORMATION4
    CONTRAINDICATIONS
    • ORILISSA is contraindicated in women who are pregnant (exposure to ORILISSA early in pregnancy may increase the risk of early pregnancy loss), in women with known osteoporosis or severe hepatic impairment, in women taking organic anion transporting polypeptide (OATP) 1B1 inhibitors that are known or expected to significantly increase elagolix plasma concentrations, and in women with known hypersensitivity reaction to ORILISSA or any of its inactive components. Reactions have included anaphylaxis and angioedema.
    WARNINGS AND PRECAUTIONS
    Bone Loss
    • ORILISSA causes a dose-dependent decrease in bone mineral density (BMD), which is greater with increasing duration of use and may not be completely reversible after stopping treatment.
    • The impact of ORILISSA-associated decreases in BMD on long-term bone health and future fracture risk is unknown. ORILISSA is contraindicated in women with known osteoporosis. Consider assessment of BMD in patients with a history of low-trauma fracture or other risk factors for osteoporosis or bone loss.
    • Limit the duration of use to reduce the extent of bone loss.
    Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy
    • Women who take ORILISSA may experience a reduction in the amount, intensity, or duration of menstrual bleeding, which may reduce the ability to recognize the occurrence of pregnancy in a timely manner. Perform pregnancy testing if pregnancy is suspected, and discontinue ORILISSA if pregnancy is confirmed.
    Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders
    • Suicidal ideation and behavior, including one completed suicide, occurred in subjects treated with ORILISSA in the endometriosis clinical trials.
    • ORILISSA users had a higher incidence of depression and mood changes compared to placebo and ORILISSA users with a history of suicidality or depression had an increased incidence of depression. Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits. Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate.
    • Advise patients to seek immediate medical attention for suicidal ideation and behavior. Reevaluate the benefits and risks of continuing ORILISSA if such events occur.
    Hepatic Transaminase Elevations
    • In clinical trials, dose-dependent elevations of serum alanine aminotransferase (ALT) at least 3 times the upper limit of the reference range occurred with ORILISSA.
    • Use the lowest effective dose and instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury, such as jaundice.
    • Promptly evaluate patients with elevations in liver tests to determine whether the benefits of continued therapy outweigh the risks.
    Interactions with Hormonal Contraceptives
    • Advise women to use effective non-hormonal contraceptives during treatment and for 28 days after discontinuing ORILISSA.
    • Coadministration of ORILISSA 200 mg twice daily with an estrogen-containing contraceptive is not recommended because of the potential for increased estrogen-associated risks including thromboembolic disorders and vascular events. Coadministration of ORILISSA with an estrogen-containing contraceptive is expected to reduce the efficacy of ORILISSA.
    • Coadministration with progestin-containing oral contraceptives may reduce the efficacy of the contraceptive. The effect of progestin-only contraceptives on the efficacy of ORILISSA is unknown. Coadministration of ORILISSA with progestin-containing intrauterine contraceptive systems has not been studied.
    ADVERSE REACTIONS
    • The most common adverse reactions (>5%) in clinical trials included hot flushes and night sweats, headache, nausea, insomnia, amenorrhea, anxiety, arthralgia, depression-related adverse reactions, and mood changes.

    These are not all the possible side effects of ORILISSA.

    Safety and effectiveness of ORILISSA in pediatric patients have not been established.

    Please click here for full Prescribing Information.