Endosis

A. Approved Indications

• Endometriosis
• Management of pelvic pain and suppression of endometrial lesions
• Contraception (in combination with estrogens)
• As a component of combined oral contraceptives (e.g., with ethinylestradiol)

B. Clinically Accepted Off-label Uses

• Adenomyosis (pain management and lesion control)
• Heavy Menstrual Bleeding (non-structural causes)
• Polycystic Ovary Syndrome (PCOS) with menstrual irregularity (with caution)
• Ovarian Endometrioma (size reduction and symptom control)
• Hormone replacement regimens (progestin component in estrogen therapy)

Route: Oral

Adults:

• Endometriosis (monotherapy):
• 2 mg once daily, taken continuously (without a break) at the same time each day
• Tablets should be taken regardless of menstrual bleeding
• Recommended duration: 3–6 months or longer based on clinical need
• Contraception (in combination):
• Usually 2 mg dienogest + 0.03 mg ethinylestradiol
• One tablet daily for 21 days, followed by 7-day tablet-free interval

Pediatrics:

• Not recommended for patients under 18 years for endometriosis monotherapy without specialist supervision

Elderly:

• Not applicable; not indicated for postmenopausal women

Renal/Hepatic Impairment:

• Hepatic impairment: Contraindicated in moderate to severe liver disease
• Renal impairment: Use with caution; no routine dose adjustment required

Dienogest is a selective progestin with potent progestogenic activity and antiandrogenic effects. It binds to progesterone receptors in endometrial tissues, resulting in suppression of estradiol-induced proliferation. It reduces gonadotropin secretion via negative feedback on the hypothalamic-pituitary axis, thereby lowering ovarian estrogen production. This estrogen suppression leads to decidualization and subsequent atrophy of endometriotic implants. Its moderate antiandrogenic activity also contributes to acne improvement and reduction of androgenic symptoms in women.

• Absorption: Rapid and nearly complete after oral administration
• Bioavailability: ~91%
• Peak Plasma Concentration: ~1.5–2 hours after oral dose
• Protein Binding: >90%, primarily to albumin (not SHBG or CBG)
• Metabolism: Extensively metabolized in the liver via CYP3A4 to inactive metabolites
• Half-life: ~9–10 hours
• Elimination: Primarily renal (as metabolites); minor fecal excretion
• Steady-State: Achieved within 4 days of daily dosing

• Pregnancy:
• Not indicated during pregnancy
• FDA Pregnancy Category: Not assigned (formerly Category X)
• Should be discontinued immediately if pregnancy occurs
• Lactation:
• Excreted into breast milk in small amounts
• Use not recommended during breastfeeding; consider alternative contraception

• Primary Class: Progestin
• Subclass: 19-nortestosterone derivative; Antiandrogenic progestogen

• Known hypersensitivity to dienogest or formulation excipients
• Active or past history of venous thromboembolism
• Arterial or cardiovascular disease (e.g., stroke, MI)
• Known or suspected hormone-sensitive malignancies (e.g., breast cancer)
• Severe hepatic impairment or active liver disease
• Undiagnosed vaginal bleeding
• Pregnancy or suspected pregnancy

• Thromboembolism Risk: Although lower than combined oral contraceptives, use cautiously in high-risk patients
• Liver Function: Monitor in long-term users; contraindicated in hepatic dysfunction
• Mood Changes/Depression: Monitor for mood disorders, especially in those with history of depression
• Bone Density: Long-term use may reduce bone mineral density; evaluate in adolescent users or at-risk adults
• Breast Cancer History: Avoid in patients with current or past hormone-sensitive tumors
• Breakthrough Bleeding: Common during initial months; generally self-limited

Common:

• Menstrual irregularities (spotting, amenorrhea)
• Headache
• Breast discomfort
• Mood changes (irritability, depression)
• Acne (can improve or worsen)
• Abdominal pain or bloating
• Nausea

Less Common:

• Weight gain or loss
• Decreased libido
• Alopecia
• Fatigue

Serious/Rare:

• Thromboembolic events (very rare)
• Hepatic dysfunction
• Severe depression or suicidal ideation
• Allergic reactions (urticaria, angioedema)

• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort): May reduce efficacy
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase dienogest levels
• Oral anticoagulants (e.g., warfarin): Monitor INR closely
• Other hormonal therapies: May antagonize or amplify effects
• Alcohol: No specific interaction, but caution advised if mood changes occur

• NICE and European Endometriosis Guidelines endorse dienogest as a first-line or maintenance therapy for endometriosis-associated pain
• Long-term Use: New recommendations advise monitoring bone density in adolescent and premenopausal users receiving prolonged therapy
• EMA and FDA maintain guidance on cautious use in women with depression and thrombotic risks

• Temperature: Store below 30°C (86°F)
• Humidity: Protect from moisture; keep in original packaging
• Light Protection: Store away from direct light
• Handling: No special handling precautions; keep out of reach of children
• Shelf-life: Typically 3 years if stored properly