Important Safety Information about ANGELIQ®
Indications and Usage:
ANGELIQ (0.25 mg drsp/0.5 mg E2) tablets and ANGELIQ (0.5 mg drsp/1.0 mg E2) are indicated for the treatment of moderate to severe vasomotor symptoms due to menopause in women who have a uterus.
In addition, ANGELIQ 0.5 mg drsp/1.0 mg E2 is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause in women who have a uterus. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
IMPORTANT SAFETY INFORMATION
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER,
and PROBABLE DEMENTIA
Estrogen Plus Progestin Therapy
Cardiovascular Disorders and Probable Dementia
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.
The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins.
Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Patients who should not take ANGELIQ:
ANGELIQ is contraindicated in women with undiagnosed abnormal genital bleeding; known, suspected or history of breast cancer; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism, or arterial thromboembolic disease (eg, stroke, myocardial infarction) or history of these conditions; renal impairment; known liver impairment or disease; adrenal insufficiency; known protein C, protein S, or antithrombin deficiency, or other thrombophilic disorders; known or suspected pregnancy; or known anaphylactic reaction, angioedema, or hypersensitivity to ANGELIQ or any of its ingredients.
Serious risks associated with ANGELIQ include:
- Cardiovascular Disorders: Estrogen/progestin therapy has been associated with an increased risk of PE, DVT, stroke, and MI. Discontinue ANGELIQ if any of these occur or are suspected. If feasible, ANGELIQ should be discontinued at least 4 to 6 weeks before any surgery associated with an increased risk of thromboembolism, or during prolonged immobilization
- Hyperkalemia: ANGELIQ contains drospirenone that has the potential for hyperkalemia in high-risk patients and is contraindicated in patients with conditions that predispose to hyperkalemia. Use caution when prescribing ANGELIQ to women who regularly take other medications that can increase potassium, such as NSAIDs, potassium-sparing diuretics, potassium supplements, ACE inhibitors, angiotensin-II receptor antagonists, heparin and aldosterone antagonists. Consider checking serum potassium concentrations during the first month of dosing in high-risk patients
- Malignant Neoplasms: The use of estrogen plus progestin therapy by postmenopausal women has been reported to increase the risk of invasive breast cancer. The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Estrogens with or without progestin may increase the risk of ovarian cancer
- Probable Dementia: Estrogens with and without progestins may increase the risk of dementia. ANGELIQ should not be used for the prevention of dementia
- Gallbladder Disease: An increased risk of gallbladder disease requiring surgery has been reported in postmenopausal women receiving estrogens
- Hypercalcemia: Estrogens may lead to severe hypercalcemia in women with breast cancer and bone metastases. If hypercalcemia occurs, discontinue ANGELIQ
- Visual Abnormalities: Discontinue ANGELIQ if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued
- Hypertriglyceridemia: Increased plasma triglycerides leading to pancreatitis may occur with estrogen therapy in women with pre-existing hypertriglyceridemia. Discontinue ANGELIQ if pancreatitis occurs
- Cholestatic Jaundice: For women with a history of cholestatic jaundice associated with past estrogen use or pregnancy, use caution and in the case of recurrence, discontinue ANGELIQ
- Hypothyroidism: Increased thyroid-binding globulin concentrations may occur. Monitor thyroid function in women on thyroid replacement therapy
- Fluid Retention: Estrogens and progestins may cause fluid retention; monitoring may be warranted in women with conditions that might be affected (eg, cardiac or renal impairment)
- Hyponatremia: As an aldosterone antagonist, drospirenone may increase the possibility of hyponatremia in high-risk patients
- Exacerbation of Other Conditions: Estrogens may exacerbate endometriosis, hereditary angioedema, asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, otosclerosis, chorea minor, and hepatic hemangiomas
Most common adverse reactions in ANGELIQ clinical trials include:
- The most common adverse reactions (≥1%) in clinical trials with different dose formulations of ANGELIQ containing E2 (0.5 mg - 1 mg) and drsp (0.25 mg - 3 mg) were gastrointestinal and abdominal pain, female genital tract bleeding, breast pain/discomfort, and headache
- The most common adverse reactions (>2%) with ANGELIQ 0.25 mg drsp/0.5 mg E2 and at a higher incidence than placebo were gastrointestinal and abdominal pains, headache, vulvovaginal fungal infections, breast pain, nausea, diarrhea, and peripheral edema