Estradiol/Drospirenone
Pronouncation: (ES-tra-dye-ole/droh-SYPE-re-none)
Class: Estrogen and progestin combined
Trade Names:
Angeliq
- Tablets estradiol 1 mg/drospirenone 0.5 mg
Indications and Usage
Treatment of moderate to severe vasomotor symptoms associated with menopause; treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.
Contraindications
Known or suspected pregnancy; undiagnosed abnormal genital bleeding; known, suspected, or history of cancer of the breast; known or suspected estrogen-dependent neoplasm; active deep vein thrombosis, pulmonary embolism, or history of these conditions; active or recent (eg, within past year) arterial thromboembolic disease (eg, MI, stroke); renal insufficiency; liver dysfunction or disease; adrenal insufficiency; hypersensitivity to any component of the product.
Dosage and Administration
Adults
PO 1 tablet daily.
Storage/Stability
Store at 59° to 86°F.
Drug Interactions
Corticosteroids
May result in an increase in the pharmacologic and toxicologic effects of corticosteroids.
Drugs affecting electrolytes (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, NSAIDs)
Potential increase in serum potassium.
Hydantoins (eg, phenytoin)
Possible loss of seizure control.
Inducers of CYP3A4 (eg, carbamazepine, modafinil, NNRT inhibitors [eg, nevirapine], phenobarbital, phenytoin, rifampin, St. John's wort)
Estrogen plasma concentrations may be reduced, decreasing the therapeutic effects and changing the uterine bleeding profile.
Inhibitors of CYP3A4 (eg, clarithromycin, erythromycin, grapefruit juice, itraconazole, ketoconazole, ritonavir)
Estrogen plasma concentrations may be elevated, increasing the risk of adverse reactions.
Thyroid hormones
Serum-free thyroxine concentration may be decreased, increasing the need for thyroid hormone.
Topiramate
May reduce estrogen concentration, decreasing the efficacy.
Laboratory Test Interactions
Decreased
Decreased antithrombin III activity; decreased levels of anti-factor Xa and antithrombin III; decreased free hormone concentrations; impaired glucose tolerance; reduced LDL; reduced response to metyrapone test; T 3 resin uptake is decreased.
Increased
Increased activated partial thromboplastin time, platelet aggregation time, and PT; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulation activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta thromboglobulin; increased levels of fibrinogen activity; increased plasminogen antigen and activity; increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone; increased corticosteroid binding globulin; increased sex hormone binding globulin; increased angiotensinogen/rennin substrate, alpha-1-antitrypsin, ceruloplasmin; increased TBG and levels of various other lipids and lipoproteins may be affected.
Adverse Reactions
Cardiovascular
Deep and superficial venous thrombosis; increased BP; MI; pulmonary embolism; stroke; thrombophlebitis.
CNS
Headache (10%); changes in libido; chorea; dementia; dizziness; exacerbation of epilepsy; irritability; mental depression; migraine; mood disturbances; nervousness.
Dermatologic
Chloasma or melasma; erythema multiforme; erythema nodosum; hemorrhagic eruption; hirsutism; loss of scalp hair; pruritus; rash.
EENT
Intolerance to contact lenses; retinal vascular thrombosis.
GI
Abdominal pain (11%); enlarged abdomen (7%); abdominal cramps; bloating; gallbladder disease; nausea; pancreatitis; vomiting.
Genitourinary
Breast pain (19%); vaginal hemorrhage (9%); endometrial disorder (2%); leukorrhea (1%); abnormal withdrawal bleeding or flow; breakthrough bleeding; breast cancer; breast enlargement, pain, and tenderness; changes in amount of cervical secretion, cervical ectropion, or vaginal bleeding pattern; dysmenorrhea; endometrial cancer; endometrial hyperplasia; fibrocystic breast changes; galactorrhea; increased size of uterine leiomyomata; nipple discharge; ovarian cancer; spotting; vaginitis, including vaginal candidiasis.
Hepatic
Cholestatic jaundice; enlargement of hepatic hemangiomas.
Metabolic
Peripheral edema (2%).
Metabolic-Nutritional
Hypocalcemia; increased triglycerides; increased weight; reduced carbohydrate tolerance.
Musculoskeletal
Back pain (7%); arthralgia; leg cramps.
Respiratory
Upper respiratory tract infection (19%); sinusitis (5%).
Miscellaneous
Pain in extremities (8%); decreased weight, flu syndrome (7%); accidental injury (6%); surgery (5%); aggravation of porphyria; anaphylactic/anaphylactoid reactions, including angioedema and urticaria; edema; exacerbation of asthma.
Precautions
Warnings
Do not use estrogens for prevention of CV disease or dementia. The Women's Health Initiative study reported increased risks of MI, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 yr of treatment with oral conjugated estrogens combined with medroxyprogesterone. In addition, increased risk of developing probable dementia in postmenopausal women 65 yr of age and older during 5.2 yr of treatment with conjugated estrogens alone and during 4 yr of treatment with oral conjugated estrogens plus medroxyprogesterone was reported. Although the combination of estradiol/drospirenone was not studied, in the absence of comparable data, assume these risks are similar. Because of these risks, prescribe estrogens with or without progestins at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.
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Monitor
Monitor BP at regular intervals; monitor blood glucose levels in patients with diabetes. Consider checking potassium levels during the first treatment cycle in patients predisposed to hyperkalemia.
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Pregnancy
Category X.
Lactation
Secreted in breast milk.
Children
Not indicated for use in children.
Hepatic Function
Drospirenone Cl may be decreased, and estrogens may be poorly metabolized. Use with caution in patients with history of cholestatic jaundice associated with estrogen use or pregnancy.
Special Risk Patients
Use with caution in patients with asthma, diabetes mellitus, epilepsy, hepatic hemangiomas, migraine, porphyria, and systemic lupus erythematosus.
Elevated BP
Sustained increases in BP have been attributed to idiosyncratic reactions to estrogens.
Endometrial cancer
Use of unopposed estrogens in women with intact uteri has been associated with increased risk of endometrial cancer, which is related to the dose and duration of estrogen therapy.
Endometriosis
May be exacerbated.
Fluid retention
Carefully monitor patients with conditions that might be influenced by fluid retention (eg, cardiac or renal dysfunction) because estrogen and estrogen/progestin therapy may cause fluid retention.
Gallbladder disease
The risk of gallbladder disease requiring surgery is increased 2- to 4-fold.
Hypercalcemia
Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases.
Hyperkalemia
Do not use in patients with conditions that predispose them to hyperkalemia (eg, adrenal insufficiency, hepatic or renal function impairment).
Hypertriglyceridemia
In patients with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations in plasma triglycerides, leading to pancreatitis and other complications.
Hypocalcemia
Use with caution in patients with severe hypocalcemia.
Hyponatremia
Risk may be increased by drospirenone.
Ovarian cancer
The risk may be increased.
Visual abnormalities
Retinal vascular thrombosis may occur, leading to diplopia, loss of vision, migraine, or sudden onset of proptosis.
Overdosage
Symptoms
Altered potassium and sodium plasma concentrations, nausea, withdrawal bleeding in women.
Patient Information
- Advise patients to discuss the patient information leaflet with the health care provider.
- Advise patients to regularly (eg, every 3 to 6 mo) talk with health care provider to assess the need to continue treatment.
- Advise patients who experience breast lumps, changes in speech, changes in vision, chest pain, dizziness, faintness, leg pain, severe headache, shortness of breath, unusual vaginal bleeding, or vomiting to notify health care provider.
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