Desogestrel

A. Approved Indications

• Hormonal Contraception:
• Progestin-only contraceptive pill (POP): Indicated for the prevention of pregnancy in women of reproductive age.
• Combined oral contraceptive (COC): Used in combination with ethinylestradiol for regular contraception in women.

B. Clinically Accepted Off-Label Uses

• Menstrual disorders:
• Management of irregular cycles, heavy menstrual bleeding (menorrhagia), and painful menstruation (dysmenorrhea).
• Polycystic Ovary Syndrome (PCOS):
• For regulation of cycles and management of hyperandrogenism in COC formulations.
• Endometriosis:
• To reduce endometrial proliferation and pelvic pain.
• Acne vulgaris:
• Used in combination therapy to suppress androgens in women with moderate to severe acne.

A. Adults (Women of Reproductive Age)

• Desogestrel 75 mcg (POP):
• One tablet taken orally once daily at the same time every day, without interruption, including during menstruation.
• A delay of more than 12 hours reduces contraceptive reliability; backup contraception is advised for 48 hours.
• Combined Formulation (Desogestrel 150 mcg + Ethinylestradiol 30 mcg):
• One tablet daily for 21 consecutive days, followed by a 7-day tablet-free interval or 7 inert tablets depending on the product.

B. Pediatric Use

• Not indicated before menarche.
• Post-menarche adolescent females may use under adult guidance with standard adult dosing.

C. Geriatric Use

• Not intended for use in postmenopausal women.

D. Special Populations

• Renal impairment: No routine dose adjustment, but caution is advised due to limited data.
• Hepatic impairment: Contraindicated in severe liver dysfunction due to metabolism concerns.

Route of Administration: Oral

Duration of Therapy: Continuous daily use until contraception is no longer required or contraindicated.

Desogestrel is a third-generation synthetic progestin that, after oral ingestion, is rapidly converted in the liver to its active metabolite, etonogestrel. It primarily works by inhibiting ovulation through suppression of the luteinizing hormone (LH) surge. Additionally, it increases cervical mucus viscosity, creating a barrier to sperm penetration, and induces endometrial changes that reduce the likelihood of implantation. These mechanisms contribute to its high contraceptive efficacy, even in progestin-only formulations.

• Absorption: Rapid and nearly complete; not affected by food.
• Bioavailability: Approximately 74% to 100%.
• Time to Peak (Tmax): 1.5 to 2 hours for etonogestrel.
• Protein Binding: About 95-99%, primarily to albumin; does not bind SHBG like other progestins.
• Metabolism: Extensively metabolized in the liver via CYP3A4 to the active metabolite etonogestrel, then further to inactive forms.
• Half-Life: Approx. 30 hours for etonogestrel.
• Excretion: Eliminated mainly via urine and feces as metabolites.

• Pregnancy:
• Desogestrel is contraindicated during pregnancy. No benefit exists during confirmed pregnancy, and continued exposure is not recommended.
• Under the current FDA system, it is not assigned a letter category; risk is presumed if used inadvertently.
• Lactation:
• Considered safe for use in breastfeeding mothers.
• Only trace amounts are excreted into breast milk with no observed harmful effects on the infant’s growth or development.
• Desogestrel 75 mcg is often the preferred hormonal contraceptive during lactation.

• Primary Class: Progestin (Hormonal contraceptive)
• Subclass: 3rd Generation Progestin
• Formulations:
• Progestin-only contraceptive (POP)
• Combined oral contraceptive (COC) with ethinylestradiol

• Hypersensitivity to desogestrel or any tablet component
• Known or suspected pregnancy
• Active thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism)
• Severe liver disease or hepatic tumors
• Known or suspected estrogen- or progestin-sensitive cancer (e.g., breast cancer)
• Unexplained vaginal bleeding
• History of cerebrovascular accident or myocardial infarction
• Migraine with aura (for COC formulations)

• Thromboembolic Risk: Especially in COC formulations; monitor women with personal or family history.
• Liver Dysfunction: Avoid in patients with significant hepatic impairment or tumors.
• Breast Cancer Risk: Use with caution if personal or strong family history exists.
• Mental Health: Monitor for depressive symptoms; discontinue if severe mood disturbances occur.
• Diabetes: May slightly alter glucose tolerance; monitor in diabetic patients.
• Missed Pills: A delay over 12 hours in taking the POP reduces efficacy; strict adherence is crucial.
• Ectopic Pregnancy: Slightly increased risk with progestin-only methods; consider in cases of unexplained abdominal pain.

Common (≥1%):

• Reproductive system: Irregular bleeding, amenorrhea, breast tenderness
• Neurological: Headache, dizziness, mood swings
• Gastrointestinal: Nausea, abdominal pain

Less Common (0.1–1%):

• Acne, weight gain, libido changes

Rare (<0.1%) but Serious:

• Venous thromboembolism (mainly in COC users)
• Hepatic adenomas
• Severe allergic reactions (urticaria, angioedema)
• Depression with suicidal ideation (rare but reported)

Enzyme Inducers (↓ effectiveness):

• Rifampicin, phenytoin, carbamazepine, phenobarbital, topiramate, St. John's Wort
• Induce CYP3A4 metabolism → reduce contraceptive effectiveness → recommend backup contraception.

Enzyme Inhibitors (↑ levels):

• Ketoconazole, itraconazole, erythromycin, ritonavir
• Increase plasma concentration → higher risk of side effects.

Other Considerations:

• Antibiotics: Generally no significant interaction, but caution with enzyme-inducing types.
• Alcohol: No direct interaction, but may reduce compliance with daily dosing.

• WHO 2024 recommendations reaffirm desogestrel 75 mcg as the preferred progestin-only oral contraceptive due to higher ovulation suppression efficacy.
• CDC and UK MEC 2023 guidelines support use of desogestrel POP in women with estrogen contraindications (e.g., smokers >35, migraine with aura).
• EMA 2022 safety update confirms no new major risks identified; VTE risk remains significantly lower with POPs compared to COCs.

• Storage Temperature: Below 25°C (77°F)
• Humidity: Store in dry conditions
• Light Protection: Keep in original blister packaging to protect from light
• Handling Instructions:
• Do not refrigerate
• Keep out of reach of children
• Do not use if tablet color changes or blister is damaged