Dosing and uses of Angeliq (drospirenone-estradiol)
Adult dosage forms and strengths
drospirenone/estradioL
tablet
- 0.25mg/0.5mg
- 0.5mg/1mg
Hormone Replacement Therapy
1 tablet PO daily
Use the lowest dose that will control symptoms
Renal Impairment
Do not administer
Hepatic Impairment
Do not administer
Other Indications & Uses
Hormone replacement therapy for women with intact uterus: Treatment of menopause-associated hot flashes and vulvar/vaginal atrophy
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Hormone replacement therapy
1 tablet PO daily
Use the lowest dose that will control symptoms
Angeliq (drospirenone-estradiol) adverse (side) effects
>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
Warnings
Contraindications
Hypersensitivity
Known anaphylactic reaction or angioedema
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Pregnancy
Estrogen-dependent neoplasia
Current/history of: DVT/PE, arterial thromboembolic disease, breast cancer, liver disease/tumours
Undiagnosed abnormal vaginal bleeding
Jaundice with previous OCP use
Porphyria
History of pruritus gravidarum, pemphigoid gestationis, deterioration of otosclerosis or idiopathic jaundice during pregnancy
Untreated endometrial hyperplasia
Hepatic/renal/adrenal impairment
Cautions
Bone mineral density changes, current/history of depression, DM, HTN, hyperlipidemia, obesity, endometriosis, family history of breast cancer and 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
Consider monitoring serum potassium concentrations during first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly
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
Pregnancy and lactation
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.
Pharmacology of Angeliq (drospirenone-estradiol)
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)
