Angeliq Information
Angeliq () Description
Drospirenone, (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3´,4´,6, 6a,7,8,9,10,11,12,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-[ 17H-dicyclopropa[6,7:15,16]cyclopenta[a]phenanthrene- 17,2´(5H)-furan]-3,5´(2H)-dione (CAS) is a synthetic progestational compound and has a molecular weight of 366.5 and a molecular formula of CHO.
Estradiol USP, (Estra-1,3,5(10)-triene-3,17-diol,17ß), has a molecular weight of 272.39 and the molecular formula is CHO. The structural formulas are as follows:
Angeliq () Clinical Pharmacology
Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol (E2) is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.
Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These will vary in proportion from tissue to tissue.
Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), through a negative feedback mechanism.
Drospirenone (DRSP) is a synthetic progestin and spironolactone analog with antimineralocorticoid activity. In animals and , drospirenone has antiandrogenic activity, but no glucocorticoid, antiglucocorticoid, estrogenic, or androgenic activity. Progestins counter estrogenic effects by decreasing the number of nuclear estradiol receptors and suppressing epithelial DNA synthesis in endometrial tissue.
Angeliq () Indications And Usage
1. Treatment of moderate to severe vasomotor symptoms associated with the menopause.
2. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Angeliq () Contraindications
Progestogens/estrogens should not be used in individuals with any of the following conditions:
1. Undiagnosed abnormal genital bleeding.
2. Known, suspected, or history of cancer of the breast.
3. Known or suspected estrogen-dependent neoplasia.
4. Active deep vein thrombosis, pulmonary embolism or history of these conditions.
5. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
6. Renal insufficiency.
7. Liver dysfunction or disease.
8. Adrenal insufficiency.
9. should not be used in patients with known hypersensitivity to its ingredients.
10. Known or suspected pregnancy. There is no indication for in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy. (See ).
Angeliq () Warnings
Angeliq () Precautions
Long-term continuous administration of estrogen, with and without progestin, in women with and without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See Boxed Warnings , and .)
Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. (See Boxed Warnings , , and sections.)
In a 24 month oral carcinogenicity study in mice dosed with 10 mg/kg/day drospirenone alone or 1 + 0.01, 3 + 0.03 and 10 + 0.1 mg/kg/day of drospirenone and ethinyl estradiol, 0.24 to 10.3 times the exposure (AUC of drospirenone) of women taking a 1 mg dose, there was an increase in carcinomas of the harderian gland in the group that received the high dose of drospirenone alone. In a similar study in rats given 10 mg/kg/day drospirenone alone or 0.3 + 0.003, 3 + 0.03 and 10 + 0.1 mg/kg/day drospirenone and ethinyl estradiol, 2.3 to 51.2 times the exposure of women taking a 1 mg dose, there was an increased incidence of benign and total (benign and malignant) adrenal gland pheochromocytomas in the group receiving the high dose of drospirenone. Drospirenone was not mutagenic in a number of(Ames, Chinese Hamster Lung gene mutation and chromosomal damage in human lymphocytes) and (mouse micronucleus) genotoxicity tests. Drospirenone increased unscheduled DNA synthesis in rat hepatocytes and formed adducts with rodent liver DNA but not with human liver DNA. (See section.)
Angeliq ()
Contraindications
Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when is administered to a nursing woman.
After administration of an oral contraceptive containing drospirenone about 0.02% of the drospirenone dose was excreted into the breast milk of postpartum women within 24 hours. This results in a maximal daily dose of about 3 mcg drospirenone in an infant.
Angeliq ()
There have not been sufficient numbers of geriatric patients involved in clinical studies utilizing to determine whether those over 65 years of age differ from younger subjects in their response to .
In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n = 3,729) were 65 to 74 while 18% (n = 803) were 75 and over. Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group. Ninety percent of the cases of probable dementia occurred in the 54% of women who were older than 70. (See , .)
Angeliq () Adverse Reactions
See Boxed Warnings , , AND .
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The following are adverse events reported with occurring in >5% of subjects:
The following additional adverse reactions have been reported with
estrogen and or estrogen/progestin therapy:
Angeliq () Overdosage
In cases of overdose, monitor serum concentrations of potassium and sodium since drospirenone has antimineralocorticoid properties.
Serious ill effects have not been reported following acute ingestion of large doses of progestin/estrogen-containing oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding may occur in females.
Angeliq () Dosage And Administration
The dosage of is one tablet daily. Women who are already using a product containing estrogen should stop taking that product before starting .
Use of estrogen, alone or in combination with a progestin, should be limited to the lowest effective dose available and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (see Boxed Warnings and sections). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
The lowest effective dose of has not been determined.
Angeliq () How Supplied
3 blisters of 28 tablets NDC 50419-483-03
Storage Conditions
Store at 25° C (77° F); excursions permitted to 1530° C (5986° F) [See USP Controlled Room Temperature].
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