drospirenone/estradiol (Rx)

>10%

Breast pain (19%)

Upper respiratory infection (19%)

Abdominal pain (11%)

1-10%

Edema

Peripheral edema

Headache

Accidental injury, back pain, pain in extremity

Endometrial disorder

Leukorrhea

Vaginal hemorrhage

Abdominal enlargement

Flu syndrome

Sinusitis

Contraindications

Hypersensitivity

Undiagnosed abnormal genital bleeding

Known, suspected, or history of cancer of the breast

Known or suspected estrogen-dependent neoplasia

Active DVT, PE, or a history of these conditions

Active arterial thromboembolic disease (for example, stroke and MI), or history of these conditions

Renal impairment

Known liver impairment or disease

Adrenal insufficiency

Known or suspected pregnancy

Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Known anaphylactic reaction, angioedema, or hypersensitivity

Cautions

Use caution in bone mineral density changes, current/history of depression, DM, HTN, hyperlipidemia, obesity, endometriosis, family history of breast cancer, DVT/PE, smoking

Discontinue if the following develop: jaundice, visual problems, 4-6 wk before major surgery, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression

Increased risk of post-op thromboembolic complications, arterial/venous thromboembolic disorder, hyperkalemia, exacerbation of endometriosis

Do not use with conditions that predispose to hyperkalemia

Conditions exacerbated by fluid retention (eg, asthma, migraine, cardiac/renal dysfunction, epilepsy)

Patients on warfarin/oral anticoagulants: oestrogens increase thromboembolic risk; increase in anticoagulant dose may be warranted

History of migraine with aura

Cholelithiasis

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema

Consider topical vaginal products when used solely for vulvovaginal atrophy

Increased risk of ovarian cancer reported in women who used hormonal therapy for menopausal symptoms

Manage appropriately risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus)

A 2 to 4-fold increase in risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens reported

Retinal vascular thrombosis reported in patients receiving estrogens; discontinue medication pending examination if there is 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 discontinued

There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance

In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications

Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue medication

Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range

Use caution in individuals with severe hypocalcemia

Pregnancy Category: contraindicated in pregnancy

Lactation: enters breast milk/not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Estradiol: Endogenous estrogen; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues. Estrogen replacement reduces elevated levels of estrogen and progesterone LH and FSH in postmenopausal women

Drospirenone: Progestin; spironolactone analog with antimineralocorticoid and antiandrogenic activity

Pharmacokinetics

Half-Life elimination: 36-42 hr (drospirenone)

Vd: 4.2 L/kg (drospirenone)

Metabolism: Hepatic

Bioavailability: 76-85% (drosperidone)

Metabolites: Inactive

Excretion: Urine, feces

Peak plasma time

• Drospirenone: 1 hr
• Estradiol: 6-8 hr

Peak plasma concentration

• Drospirenone: 13-24 ng/mL
• Estradiol: 34-54 pg/mL

Protein bound

• Drospirenone: 97% bound to serum proteins (not SHBG or corticosteroid binding globulin)
• Estradiol: 98% (37% to globulin and 61% to albumin)