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|Estradiol/Drospirenone

Estradiol/Drospirenone

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

PO 1 tablet daily.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

May result in an increase in the pharmacologic and toxicologic effects of corticosteroids.

Potential increase in serum potassium.

Possible loss of seizure control.

Estrogen plasma concentrations may be reduced, decreasing the therapeutic effects and changing the uterine bleeding profile.

Estrogen plasma concentrations may be elevated, increasing the risk of adverse reactions.

Serum-free thyroxine concentration may be decreased, increasing the need for thyroid hormone.

May reduce estrogen concentration, decreasing the efficacy.

Laboratory Test Interactions

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 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

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

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Advise patients to discuss the Patient Information leaflet with the health care provider.
• Advise patients to regularly (eg, q 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.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements without consulting health care provider.
• Advise patient that follow-up visits may be necessary and to keep appointments.