Elisa

FDA-Approved Indications:

• Contraception:
• Prevention of pregnancy in women of reproductive potential.
• Acne Vulgaris (moderate):
• In females ≥14 years of age who also desire contraception.
• Premenstrual Dysphoric Disorder (PMDD):
• Treatment of PMDD in women who choose to use an oral contraceptive.
• Regulation of Menstrual Cycles:
• To improve cycle regularity and reduce menstrual-related symptoms.

Clinically Accepted Off-Label Uses:

• Polycystic Ovary Syndrome (PCOS):
• Regulation of menstruation, management of acne and hirsutism.
• Endometriosis (symptom management):
• Used to suppress ovulation and reduce endometrial proliferation.
• Dysmenorrhea (painful menstruation):
• Reduces menstrual cramps and flow by suppressing ovulation.
• Functional Ovarian Cysts:
• Prevention through suppression of follicular development.

Adults:

• Standard Formulation:
  Drospirenone 3 mg + Ethinyl Estradiol 20–30 mcg
  One tablet orally once daily for 28 days per cycle
• 21 active + 7 placebo tablets
• Or 24 active + 4 placebo tablets (depending on brand)

Start Options:

• Day 1 Start: First tablet taken on the first day of menstruation.
• Sunday Start: First tablet taken on the first Sunday after menstruation begins.

Missed Dose Guidelines:

• One missed pill: Take as soon as remembered.
• Two or more missed pills: Follow specific instructions based on cycle day and number of pills missed; backup contraception may be required.

Pediatrics:

• Approved in postmenarchal females ≥14 years for acne vulgaris with menstrual regularity established.

Elderly:

• Not indicated in postmenopausal women.

Renal Impairment:

• Contraindicated in patients with moderate to severe renal impairment (eGFR <50 mL/min) due to risk of hyperkalemia.

Hepatic Impairment:

• Contraindicated in hepatic dysfunction or hepatic tumors.

Drospirenone + Ethinyl Estradiol suppresses ovulation by inhibiting the mid-cycle surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Drospirenone, a spironolactone-derived progestin, possesses antiandrogenic and antimineralocorticoid properties. It reduces sebum production and fluid retention. Ethinyl Estradiol stabilizes the endometrial lining and enhances the contraceptive efficacy of drospirenone. Together, the combination thickens cervical mucus (impeding sperm passage), alters the endometrium (inhibiting implantation), and prevents ovulation, providing reliable contraception and hormonal regulation.

• Absorption:
• Both components are rapidly absorbed after oral administration.
• Time to peak: ~1–2 hours for both agents.
• Bioavailability:
• Drospirenone: ~76–85%
• Ethinyl Estradiol: ~38–48%
• Distribution:
• Drospirenone: ~95–97% protein-bound (to albumin)
• Ethinyl Estradiol: ~98% protein-bound
• Metabolism:
• Drospirenone: Hepatic (not significantly via CYP3A4)
• Ethinyl Estradiol: Hepatic (extensively via CYP3A4)
• Elimination Half-life:
• Drospirenone: ~30 hours
• Ethinyl Estradiol: ~24 hours
• Excretion:
• Drospirenone: Primarily fecal and urinary
• Ethinyl Estradiol: Renal and biliary excretion

• Pregnancy:
  FDA Category X.
  Contraindicated in pregnancy. No known teratogenic effects, but use provides no benefit and should be discontinued if pregnancy is confirmed.
• Lactation:
  Ethinyl estradiol may reduce milk production. Both components are excreted in small amounts into breast milk. Not recommended during breastfeeding, especially within the first 6 weeks postpartum. Progestin-only contraceptives are preferred.

• Primary Class: Combined Oral Contraceptive (COC)
• Subclasses:
• Progestin: Drospirenone (4th generation, antiandrogenic, antimineralocorticoid)
• Estrogen: Ethinyl Estradiol (synthetic estrogen)

• Known hypersensitivity to drospirenone, ethinyl estradiol, or excipients
• Pregnancy
• Renal impairment (moderate to severe)
• Hepatic dysfunction or hepatic tumors
• Adrenal insufficiency
• History or current venous thromboembolism (DVT, PE)
• Arterial thromboembolic events (stroke, myocardial infarction)
• Migraine with aura
• Uncontrolled hypertension
• Diabetes with vascular involvement
• Breast cancer or estrogen/progestin-sensitive neoplasms
• Undiagnosed abnormal genital bleeding
• Smokers ≥35 years of age (due to increased VTE risk)

• Thromboembolic Disorders:
  Increased risk of DVT, PE, stroke, especially in smokers over 35 or women with other risk factors.
• Hyperkalemia Risk:
  Due to drospirenone’s aldosterone antagonism. Monitor potassium in patients using other potassium-sparing drugs (e.g., ACE inhibitors, NSAIDs, spironolactone).
• Hypertension:
  May cause slight increases in blood pressure; contraindicated in uncontrolled hypertension.
• Hepatic Effects:
  Discontinue if jaundice, hepatocellular injury, or significant liver enzyme elevation occurs.
• Carcinoma Risk:
  Avoid in women with current or past history of breast or estrogen-sensitive cancers.
• Mood Changes/Depression:
  Monitor for worsening depression or mood disorders.
• Migraine with Aura:
  Increased risk of stroke—discontinue use.

Common:

• Gastrointestinal: Nausea, vomiting, bloating
• Reproductive: Irregular bleeding, amenorrhea, breast tenderness
• CNS: Headache, mood swings, fatigue
• Dermatologic: Acne (may improve), skin rash
• General: Weight changes, fluid retention

Serious/Rare:

• Cardiovascular: VTE, stroke, myocardial infarction
• Hepatic: Hepatitis, cholestatic jaundice, hepatic adenoma
• Endocrine: Hyperkalemia, adrenal suppression
• Oncologic: Breast or cervical cancer (long-term use, debated)
• Allergic: Hypersensitivity reactions

• Potassium-Retaining Agents (e.g., spironolactone, ACE inhibitors, ARBs, NSAIDs):
  May increase serum potassium levels.
• CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine):
  May decrease contraceptive efficacy by increasing metabolism of ethinyl estradiol.
• CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin):
  May increase plasma levels of ethinyl estradiol.
• Antibiotics:
  Rifampin may reduce efficacy. Other antibiotics less likely to affect absorption significantly.
• HIV Medications (protease inhibitors, NNRTIs):
  May alter hormone levels; consult specific product interactions.
• Lamotrigine:
  May decrease lamotrigine levels and reduce seizure control.

• Labeling Updates:
  Recent formulations emphasize lower estrogen doses (e.g., 20 mcg EE) to minimize thrombotic risk.
• Safety Updates:
  Black box warning reinforced for thromboembolic events in high-risk groups (e.g., smokers ≥35 years).
• Clinical Recommendations:
  COCs containing drospirenone are preferred in women with acne, PCOS, or who are sensitive to estrogen-induced bloating due to its antimineralocorticoid action.
• WHO & NICE Guidelines:
  Recognize safety and efficacy in contraception, acne, and PMDD treatment. Caution advised for thrombotic risk patients.

• Temperature Range:
  Store at 20°C to 25°C (68°F to 77°F)
  Allowable excursion: 15°C to 30°C (59°F to 86°F)
• Humidity:
  Store in a dry environment; protect from excessive moisture.
• Light:
  Protect from light. Keep tablets in original blister pack until use.
• Handling Precautions:
  Keep out of reach of children. Do not use expired or damaged tablets.