Drospirenone

FDA-Approved Indications:

• Contraception
• Prevention of pregnancy as a progestin-only oral contraceptive or in combination with ethinylestradiol.
• Acne Vulgaris (moderate):
• In females ≥14 years of age seeking contraception.
• Premenstrual Dysphoric Disorder (PMDD):
• In women who choose to use an oral contraceptive for contraception.
• Menopausal Hormone Therapy (combined with estrogen):
• Management of vasomotor symptoms and prevention of postmenopausal osteoporosis.

Clinically Accepted Off-Label Uses:

• Polycystic Ovary Syndrome (PCOS):
• For cycle regulation, acne, and hirsutism.
• Hyperandrogenism:
• Reducing symptoms such as oily skin, acne, and male-pattern hair growth in women.
• Endometriosis:
• For symptom control in combination hormonal therapy.
• Functional Ovarian Cysts:
• As part of combined hormonal contraceptive regimens.

Adults (Contraceptive Use):

• Combined (with ethinylestradiol):
• 3 mg drospirenone + 20–30 mcg ethinylestradiol:
  One tablet daily for 24–28 days (regimen-dependent), ideally at the same time each day.
• Progestin-only (4 mg drospirenone):
• One tablet daily without a pill-free interval; 28-day cycles continuously.

PMDD and Acne:

• Same dosage as above with combined formulations (e.g., 3 mg drospirenone + 20 mcg ethinylestradiol).

Menopausal Hormone Therapy:

• 0.5–2 mg drospirenone daily combined with 1 mg estradiol.

Pediatrics:

• Not approved for use before menarche. For acne: approved in females ≥14 years with menstruation established.

Elderly:

• Not indicated postmenopause except in combination hormone therapy for symptom relief or osteoporosis prevention.

Renal Impairment:

• Contraindicated in moderate to severe renal impairment (eGFR <50 mL/min/1.73 m²) due to hyperkalemia risk.

Hepatic Impairment:

• Contraindicated in hepatic disease or hepatic tumors.

Administration Notes:

• Tablets should be taken at the same time each day.
• Missed doses: Take as soon as remembered. If >24 hours pass, follow backup contraception guidance.

Drospirenone is a synthetic progestin structurally related to spironolactone with both progestogenic and antiandrogenic activity. It works by binding to progesterone receptors in the hypothalamus and pituitary, inhibiting the release of gonadotropins (FSH and LH), which suppresses ovulation. It also induces changes in the endometrium and cervical mucus that prevent fertilization and implantation. Additionally, its anti-mineralocorticoid effect counteracts estrogen-induced fluid retention, and its antiandrogenic action reduces acne and hirsutism.

• Absorption: Rapid and nearly complete; peak plasma concentration reached in 1–2 hours.
• Bioavailability: ~76–85%
• Distribution: Extensive; volume of distribution ~4 L/kg; ~95–97% protein-bound (primarily albumin).
• Metabolism: Extensively metabolized in the liver (non-CYP-mediated hydrolysis and oxidation).
• Half-life: Terminal half-life ~30 hours.
• Excretion: ~38% in urine and ~58% in feces, primarily as metabolites.
• Onset of Action: Ovulation suppression occurs within 1–2 days of dosing.

• Pregnancy:
  FDA Pregnancy Category X. Contraindicated during pregnancy due to no therapeutic use. No evidence of teratogenicity, but exposure should be avoided.
• Lactation:
  Present in breast milk in small amounts. Progestin-only formulations (4 mg drospirenone) are generally considered compatible with breastfeeding, but close infant monitoring is advised, especially in preterm or low-birth-weight infants.

• Primary Class: Hormonal Contraceptive
• Subclass: Progestin (spironolactone-derived, fourth-generation)

• Known hypersensitivity to drospirenone or any formulation component
• Renal impairment (moderate to severe; eGFR <50 mL/min)
• Hepatic dysfunction or hepatic tumors (benign or malignant)
• Adrenal insufficiency
• Known or suspected pregnancy
• Undiagnosed vaginal bleeding
• History or current thromboembolic disorders (for combined estrogen formulations)

• Hyperkalemia: Monitor potassium in patients with renal impairment or those taking potassium-sparing medications.
• Venous and Arterial Thromboembolism (VTE/ATE): Increased risk in combination estrogen use; assess risk factors.
• Hypertension: Can increase blood pressure; monitor regularly.
• Breast Cancer: Hormonal contraceptives may slightly increase risk; avoid in active breast cancer.
• Liver Dysfunction: Avoid use in any hepatic disease.
• Mood Disorders: Monitor for depression or mood changes; discontinue if symptoms worsen.
• Migraine with Aura: Increased risk of stroke with estrogen-containing products.

Common:

• Reproductive: Irregular bleeding, amenorrhea, breast tenderness
• CNS: Headache, mood swings, depression
• GI: Nausea, abdominal pain
• Skin: Acne (in some users), rash
• General: Weight gain, fatigue

Serious/Rare:

• Cardiovascular: Deep vein thrombosis, pulmonary embolism, stroke (especially with estrogen)
• Endocrine: Hyperkalemia
• Hepatic: Cholestatic jaundice, hepatic adenomas
• Allergic: Anaphylaxis (rare)
• Neurologic: Migraine exacerbation, visual disturbances

• Potassium-sparing agents: (e.g., spironolactone, ACE inhibitors, ARBs, NSAIDs) → Risk of hyperkalemia.
• CYP3A4 inducers: (e.g., rifampin, carbamazepine, phenytoin) → May reduce contraceptive efficacy.
• CYP3A4 inhibitors: (e.g., ketoconazole, itraconazole) → May increase drospirenone levels.
• Antibiotics: Rifampin and griseofulvin may reduce efficacy; routine antibiotics less concerning.
• Anticoagulants: Monitor closely; estrogen-containing formulations may antagonize effects.

• Progestin-only 4 mg drospirenone formulation is now considered a safer option for women with contraindications to estrogen (e.g., smokers >35, migraine with aura).
• FDA Labeling Change (recent years): Strengthened warning on hyperkalemia and drug interaction with renal-active drugs.
• NICE & WHO Guidelines: Acknowledge drospirenone's role in acne and PCOS when contraception is also needed.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C.
• Humidity: Store in a dry place; avoid high humidity.
• Light: Protect from excessive light exposure.
• Handling: No special handling precautions; blister packaging should remain intact until use.