Ethinyl Estradiol + Gestodene

Approved Indications:

• Contraception (birth control):
  Indicated for the prevention of pregnancy in women of reproductive age through inhibition of ovulation and alteration of cervical mucus and endometrial lining.

Clinically Accepted Off-Label Uses:

• Polycystic Ovary Syndrome (PCOS):
  Used to regulate menstrual cycles, reduce androgen levels, and manage hirsutism and acne.
• Acne vulgaris (moderate to severe):
  Used in women who desire oral contraception and need additional anti-androgenic effect for acne control.
• Menstrual disorders:
  For management of dysmenorrhea, menorrhagia, and cycle irregularities.
• Endometriosis (symptom relief):
  Used to reduce pain and suppress endometrial growth.

Adults (Women of Reproductive Age):

• Standard Dose:
  One tablet daily for 21 consecutive days followed by a 7-day tablet-free interval. A new cycle starts on day 29, regardless of menstrual bleeding.
• Common Strengths per Tablet:
  Ethinyl Estradiol 0.02 mg + Gestodene 0.075 mg (commonly used combination)
• Initiation:
  Start on Day 1 of menstruation (preferred) or Day 2–5 (with additional contraception for 7 days if not starting on Day 1).
• Missed Dose Guidance:
  One missed pill: take as soon as remembered.
  Two or more missed: refer to specific product instructions and use backup contraception.

Special Populations:

• Pediatrics:
  Not indicated before menarche.
• Elderly:
  Not indicated for postmenopausal women.
• Hepatic Impairment:
  Contraindicated in severe liver disease.
• Renal Impairment:
  Use with caution; no specific adjustment guidelines.

Route of Administration: Oral

Ethinyl Estradiol, a synthetic estrogen, and Gestodene, a third-generation progestin, act synergistically to suppress the hypothalamic-pituitary-ovarian axis. Ethinyl Estradiol inhibits the secretion of follicle-stimulating hormone (FSH), preventing follicular development, while Gestodene inhibits luteinizing hormone (LH) surge, thereby preventing ovulation. Together, they induce changes in cervical mucus (making it impermeable to sperm) and alter the endometrial lining to reduce the likelihood of implantation.

• Absorption:
  Both components are well absorbed orally.
  Ethinyl Estradiol: Bioavailability ~40–45% (significant first-pass metabolism)
  Gestodene: Bioavailability ~99%
• Distribution:
  Ethinyl Estradiol: ~95–98% protein-bound (mainly albumin)
  Gestodene: ~60% binds to SHBG, 40% to albumin
• Metabolism:
  Ethinyl Estradiol: Extensively metabolized in the liver via CYP3A4, forming inactive conjugates.
  Gestodene: Metabolized primarily by CYP3A4 into inactive metabolites.
• Elimination:
  Ethinyl Estradiol: Half-life ~13–27 hours; excreted in urine and feces.
  Gestodene: Half-life ~13–20 hours; excreted in urine and bile.
• Steady-State:
  Achieved within 5–7 days of daily administration.

• Pregnancy:
  Contraindicated in pregnancy.
  Discontinue immediately if pregnancy is confirmed. No teratogenic risk has been demonstrated, but unnecessary exposure should be avoided.
• Lactation:
  Not recommended during breastfeeding, especially during the first 6 weeks postpartum. Ethinyl Estradiol may reduce milk production and pass into breast milk in small amounts. If necessary, consider non-estrogenic contraceptive methods.

• Primary Class: Combined Oral Contraceptive (COC)
• Subclass: Low-dose monophasic COC, third-generation progestin-based contraceptive

• Known hypersensitivity to Ethinyl Estradiol, Gestodene, or any excipients
• History of or current venous thromboembolism (VTE) or arterial thrombotic disorders (e.g., stroke, myocardial infarction)
• Known thrombophilic conditions (e.g., Factor V Leiden)
• Migraine with aura
• Uncontrolled hypertension
• Severe hepatic impairment or active liver disease
• Current or history of estrogen- or progestin-sensitive malignancies (e.g., breast cancer)
• Undiagnosed abnormal genital bleeding
• Pregnancy or suspected pregnancy
• Smokers over age 35 (due to elevated cardiovascular risk)

• Cardiovascular Risks:
  Increased risk of VTE, especially in women with additional risk factors (e.g., obesity, immobility, age >35, smoking).
• Cancer Risk:
  Slightly increased risk of breast and cervical cancer with prolonged use.
• Liver Function:
  Monitor in patients with a history of liver disease. Discontinue if jaundice or significant liver enzyme elevations occur.
• Depression and Mood Changes:
  Monitor patients with a history of mood disorders.
• Monitoring:
  Blood pressure, liver function tests, lipid profile, and signs of thromboembolism.
• Discontinue Immediately If:
  Severe chest pain, vision loss, migraine with aura, or signs of DVT/PE develop.

Common (≥1%):

• Headache
• Nausea, vomiting
• Breast tenderness
• Weight gain
• Breakthrough bleeding or spotting
• Mood swings or depression
• Decreased libido

Less Common:

• Fluid retention
• Acne
• Changes in appetite
• Melasma or other skin pigmentation changes

Serious/Rare:

• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Stroke or myocardial infarction
• Liver adenoma or hepatic dysfunction
• Anaphylactic reactions (rare)

Onset:
Most mild side effects occur within the first 1–3 months and often subside with continued use.

• CYP3A4 Inducers (↓ efficacy):
  Rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s Wort
  → Risk of contraceptive failure; use backup method.
• CYP3A4 Inhibitors (↑ levels):
  Ketoconazole, ritonavir → May increase adverse effects.
• Antibiotics:
  Broad-spectrum antibiotics may reduce gut flora and impair estrogen recycling (controversial but precautionary backup method advised with certain antibiotics like rifampicin).
• Anticoagulants:
  May reduce the effect of warfarin due to altered coagulation factor levels.
• Lamotrigine:
  COC may decrease lamotrigine levels, reducing seizure control.

• EMA and WHO (last 3 years):
  Emphasize patient education regarding thrombotic risks, especially with third-generation progestins like Gestodene.
• Updated Prescribing Information:
  Enhanced labeling on risks of VTE and migraine-related contraindications.
• FDA:
  No recent dosage changes; continues to support use in approved populations with individualized risk assessment.

• Temperature: Store below 25°C (77°F)
• Humidity: Protect from moisture
• Light Protection: Store in original packaging to shield from light
• Handling: Keep in a dry place; do not refrigerate or freeze
• Special Instructions: Keep out of reach of children; discard after expiration date printed on the pack