Ulipristal
Ulipristal acetate
Generic Name
Ulipristal acetate
Mechanism
Ulipristal acetate functions as a partial agonist/antagonist of the progesterone receptor (PR).
• Pre‑ovulatory phase: Antagonizes PR on the pituitary, delaying or preventing the LH surge, thereby inhibiting ovulation even when administered up to 120 h after unprotected intercourse.
• Post‑ovulatory phase: Inhibits endometrial progesterone action, altering the stromal environment and reducing implantation potential.
• Heavy menstrual bleeding: Modulates PR in endometrial decidual cells, decreasing angiogenesis and prostaglandin synthesis, which reduces menstrual flow.
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral tablet → ~99 % bioavailability; peak concentration (C_max) at 2–3 h. |
| Distribution | Protein binding ~78 % (predominantly to albumin). |
| Metabolism | Hepatic CYP3A4 and CYP2C19; forms active metabolite (U). |
| Elimination | Biliary/fecal (≈90 %) retains a terminal half‑life of ~38 h. |
| Drug Interactions | Strong CYP3A4 inducers (rifampin, carbamazepine) ↓ serum levels; inhibitors (ketoconazole) ↑ levels. |
| Special Populations | No dosage adjustment for age, sex, or mild‑moderate renal impairment; caution with severe hepatic disease. |
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Indications
- Emergency Contraception: Single 30 mg oral dose up to 120 h after unprotected intercourse (more effective than levonorgestrel beyond 72 h).
- Treatment of Heavy Menstrual Bleeding (HMB): 150 mg orally once daily ∙ 3 months, then 150 mg 3 × monthly (or 150 mg daily for 3 months in younger women).
- Progestin‑Responsive Precancerous Endometrial Lesions: Limited evidence, off‑label in certain jurisdictions.
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Contraindications
- Contraindications
- Current pregnancy or suspicion of pregnancy.
- Known or suspected hepatic disease (ALT > 5× ULN).
- Pregnant or lactating women.
- History of thromboembolic events (deep venous thrombosis, pulmonary embolism).
- Warnings
- Hepatotoxicity: Elevated transaminases (≥3 × ULN). Monitor LFTs pre‑ and post‑treatment.
- Endometrial Hyperplasia: Rare, uterine bleeding may signal abnormal histology.
- Drug–Drug Interactions: Concomitant CYP3A4 inducers may reduce efficacy; inhibitors may increase adverse effects.
- Precautions
- Baseline pregnancy test to rule out ongoing pregnancy.
- Evaluate for risk of blood clots (obesity, smoking, hormone-containing birth control).
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Dosing
| Indication | Dose | Timing | Notes |
| Emergency Contraception | 30 mg | Oral, single dose ≤ 120 h (ideally within 72 h) | Best administered as early as possible; not a contraception method. |
| Heavy Menstrual Bleeding | 150 mg | Once daily, 28 days/month; after 3 months can be 3 × monthly dosing | Take at the same time each day. |
| Special | — | — | Re‑evaluation after 2 months for HMB may permit dose reduction. |
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Adverse Effects
- Common
- Headache, nausea, abdominal pain, breast tenderness.
- Menstrual irregularities (spotting, breakthrough bleeding).
- Fatigue, dizziness.
- Serious
- Hepatic injury: Jaundice, dark urine, RUQ pain.
- Thromboembolism: Rare, usually in predisposed individuals.
- Uterine bleeding: Heavy, prolonged bleeding may require evaluation.
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Monitoring
| Parameter | Frequency | Rationale |
| Serum transaminases (ALT/AST) | Baseline; repeat 4 weeks after start (HMB); post‑EC if abnormal symptoms | Detect hepatotoxicity early. |
| Pregnancy test | Prior to EC; repeat if late bleeding | Exclude pregnancy. |
| Pregnancy history | Every prescription | Identify clotted risk. |
| Lipid panel and coagulation profile | Baseline in high‑risk patients | Evaluate clotting tendencies. |
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Clinical Pearls
- Efficacy Window: Ulipristal’s EC efficacy remains high up to 120 h; beyond 72 h, it surpasses levonorgestrel by a factor of ~5–10 % in preventing pregnancy.
- “Take‑When‑Needed”: For HMB, a bimonthly or monthly dosing schedule after the first 3 months can maintain benefit while reducing drug exposure and cost.
- Interaction with Oral Contraceptives: Ulipristal can lower the efficacy of other hormonal contraceptives when taken overlapping; advise spacing of 2 days if concurrently used.
- Headache Management: Maximize controlled pain with acetaminophen; NSAIDs may exacerbate hepatic stress—use cautiously in hepatic impairment.
- Reduced Adherence with Long-Use: Gastrointestinal discomfort may reduce compliance; consider oral sucrose‑acid (if available) to buffer mucosa.
- Endometrial Safety: While rare, histologic evaluation is recommended for any ulcerative uterine bleeding > 2 weeks after initiation.
- Pregnancy Confirmation: A negative pregnancy test is mandatory before prescribing; a urine NPU test after 6 weeks of amenorrhea may still miss early pregnancy—re‑test if doubt remains.
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• *This drug card offers concise, reference‑grade information for medical learners and clinicians. Always refer to the latest prescribing information and clinical guidelines for individualized patient care.*