Ulipristal Acetate

Ulipristal acetate is a selective progesterone receptor modulator used as an oral emergency contraceptive. It is given as 30 mg as a single dose, as soon as possible and within 120 hours of unprotected intercourse. Efficacy is better maintained across the 120 hours than with levonorgestrel. Availability must be confirmed in each facility before it is offered.

Mechanism. It delays ovulation, and it can do so after the luteinising hormone surge has begun, up to shortly before the peak. This is the main reason for its advantage over levonorgestrel near ovulation. It does not end an established pregnancy.

Pharmacokinetics. It is absorbed rapidly, with peak levels within about 2 hours, and has a half-life of about 32 hours. Metabolism is hepatic through the CYP3A4 enzyme.

Effectiveness. About 8 pregnancies in 100 women follow one act of unprotected intercourse in the fertile phase. After oral emergency contraception, 1 to 2 in 100 become pregnant. Ulipristal acetate prevents more pregnancies than levonorgestrel, especially from 72 to 120 hours.

Duration and return to fertility. Protection covers the episode treated. Ovulation is delayed, not abolished for the cycle, so a further act later in the cycle carries risk.

Best candidates. Patients 72 to 120 hours after intercourse, patients near ovulation, and patients with higher body weight who decline a copper IUD.

Category 1. Previous ectopic pregnancy, sexual assault, and obesity.

Category 2. Breastfeeding, because the drug passes into milk. Also previous ischaemic heart disease, stroke or other thromboembolic disease, angina, migraine, and severe liver disease including jaundice. Give without delay.

Contraindications. Known pregnancy and hypersensitivity. Severe asthma controlled only by oral corticosteroids calls for caution.

Interactions.

• Strong enzyme inducers (rifampicin, rifabutin, phenytoin, phenobarbital, carbamazepine, efavirenz, nevirapine, St John's wort) lower ulipristal levels and efficacy. The copper IUD is preferred. If it cannot be placed, levonorgestrel 3 mg as a single dose is used.

• Antacids, histamine-2 blockers and proton pump inhibitors may reduce absorption.

• Progestins taken in the 5 days after the dose lower its effect.

Counselling points for the clinician. Obtain consent, protect confidentiality and exclude coercion. Explain that hormonal contraception is delayed by 5 days and that condoms are needed meanwhile. Note that the dose does not protect against sexually transmitted infections or HIV.

Special groups.

• Breastfeeding: levonorgestrel is preferred. If ulipristal acetate is used, breastfeeding is withheld and milk is expressed and discarded for 1 week.

• Postpartum: not needed before 4 weeks after birth.

• Adolescents: no age limit applies.

• Liver disease: severe disease is category 2.

Regimen.

• Drug and strength: ulipristal acetate 30 mg tablet. Route: by mouth, with or without food.

• Timing: as soon as possible, within 120 hours of unprotected intercourse.

• Frequency: one dose for each episode, with no second dose for the same episode.

• Duration of protection: the episode treated only.

• Backup and switching: condoms throughout. No progestin for 5 days after the dose.

Pregnancy exclusion. Pregnancy is reasonably excluded when there has been no unprotected intercourse since the last normal menses and menses are not overdue. A test is not required before one recent episode. If menses are more than 7 days late, test.

Vomiting. Within 2 hours of the dose, repeat it with an antiemetic. If vomiting continues, place the repeat tablet high in the vagina. After more than 2 hours, give nothing further.

Starting ongoing contraception after ulipristal acetate. Wait 5 days, then start the chosen hormonal method with backup.

• Combined pills, patch, ring: backup 7 days.

• Injectable and implant: backup 7 days.

• Progestin-only pills: backup 2 days, except drospirenone pills, which need 7 days.

• Copper IUD: may be placed on the same day, with no backup.

Follow up. Advise return if menses are more than 7 days late or if there is unusual bleeding or lower abdominal pain. Menses are delayed more often than after levonorgestrel. Test 3 weeks after the episode if menses have not started.

Expected effects. Headache, nausea, abdominal pain, painful menses, dizziness and fatigue. Menses may be delayed by a few days.

Management.

• Mild nausea: reassure and advise food or milk.

• Severe nausea: ondansetron 4 mg by mouth as one dose, repeated once after 8 hours if needed. Maximum 12 mg in 24 hours, for no more than 2 days. Limit to 8 mg in 24 hours in severe liver disease. No kidney adjustment is needed. Avoid in congenital long QT syndrome. In pregnancy use only when the benefit is clear. Short courses are acceptable in breastfeeding.

• Headache: a mild analgesic if blood pressure is normal. Refer if blood pressure is high.

Failure and pregnancy. Limited data show no harm to a pregnancy from exposure. Assess for ectopic pregnancy when a positive test comes with pain or bleeding.

Common errors. Starting a progestin within 5 days of the dose, giving levonorgestrel after ulipristal acetate for the same episode, and giving the dose to a patient on strong enzyme inducers without offering the copper IUD.

Referral and escalation. Refer for severe lower abdominal pain, fainting, heavy bleeding, persistent vomiting or a positive pregnancy test with pain or bleeding.