The POM to P switch of ulipristal (ellaOne) means pharmacists will be able to help more women avoid unplanned pregnancies and enhance their position at the forefront of community sexual health services.

British women spend about 30 years trying to avoid unplanned pregnancies.¹ Yet despite 13 forms of contraception for women and two for men,² one in six (16.2 per cent) pregnancies in the UK are unplanned and 29 per cent are “ambivalent”.¹

Not surprisingly, younger women are especially likely to have unplanned pregnancies. In women aged between 16 and 19 years, almost half (45.2 per cent) of pregnancies are unplanned and only one in 10 (11.6 per cent) is planned. In women aged between 20 and 24 years, almost a fifth of pregnancies (17.4 per cent) are unplanned and more than two-fifths (42.7 per cent) are ambivalent. However, most unplanned pregnancies occur among women aged 20 to 34 years (62.4 per cent).¹

The consequences of an unplanned pregnancy can last a lifetime. It increases the risk of obstetric complications, for example. Women with unplanned pregnancies also typically present later for antenatal care than other mothers-to-be and are especially vulnerable to prenatal and postnatal depression and relationship breakdowns.

A child born after an unplanned pregnancy is at increased risk of lower birth weight as well as poorer mental health, physical health and cognitive performance.¹

About 57 per cent of women opt for terminations after unplanned pregnancies, contributing to the 185,331 abortions performed in England and Wales during 2013. While the ‘backstreet abortionists’ are long gone, abortions still carry some risks including haemorrhage (one in every 1,000 abortions, according to NHS Choices), cervical damage (one in every 100 abortions) and womb damage (one in every 250 to 1,000 surgical and medical abortions respectively).

Pharmacy and EHC

Easily accessible emergency contraception helps reduce the risks associated with unplanned pregnancies. Pharmacists have offered emergency contraception over the counter since 2001 when levonorgestrel switched from POM to P. Women need to take levonorgestrel within 72 hours of unprotected intercourse or contraceptive failure.³

The forthcoming switch of ulipristal acetate (ellaOne) from POM to P will bolster community pharmacists’ position at the forefront of community sexual health still further. Women can take ulipristal as emergency contraception within up to 120 hours (five days) of unprotected intercourse or contraceptive failure and, the evidence shows, it is more effective than levonorgestrel when taken within the first 24 hours (and also 72 hours) of unprotected sex.³

The switch therefore means that pharmacists should be able to help more women avoid unplanned pregnancies.

Different mechanism

Levonorgestrel is a synthetic progestogen, while ulipristal is a selective progesterone receptor modulator (SPRM) with a mix of agonist and antagonist actions.^4-6 It acts primarily by inhibiting or delaying ovulation.

Levonorgestrel inhibits ovulation during 83 per cent of menstrual cycles if taken when the ovarian follicle is between 12-14mm. However follicles of this size are relatively immature and the risk of conception in women with regular cycles following unprotected intercourse at this stage is less than 30 per cent.

When the follicle reaches 18-20mm, ovulation generally follows within 48 hours and the probability of conception is more than 80 per cent. Taken when the follicle reaches 18-20mm, levonorgestrel prevents ovulation in 12 per cent of cycles (compared with 13 per cent with placebo). In contrast, ulipristal prevents ovulation in 60 per cent of cycles at this stage.⁷

More effective than levonorgestrel?

Clinical studies suggest that ulipristal appears to be more effective as emergency contraception than levonorgestrel.

In one study,⁷ 844 women received a single dose of 30mg ulipristal and 852 took 1.5mg levonorgestrel within 72 hours of unprotected intercourse. The pregnancy rates were 1.8 and 2.6 per cent with ulipristal and levonorgestrel respectively, a 32 per cent reduction. Combining these results with those reported in another study, the pregnancy rates when taken within 72 hours of unprotected sex were 1.4 and 2.2 per cent with ulipristal and levo-norgestrel respectively, a 42 per cent reduction.⁷

Women should take emergency contraception as soon as possible: ulipristal is most effective when taken within 24 hours of unprotected sex.³ However, as mentioned, women can take ulipristal up to five days after unprotected sex, compared to the recommended 72 hours with levonorgestrel.

In this study, 63 and 73 women received emergency contraception with ulipristal and levonorgestrel respectively between 73 and 120 hours after unprotected sex. None of those who received ulipristal became pregnant, compared to 4 per cent of those who took levonorgestrel.⁷

Furthermore, according to the SPC, the pregnancy rate was 2.1 per cent in an open-label study that enrolled 1,241 women who took ulipristal for emergency contraception 48 to 120 hours after unprotected intercourse.

Side-effects and interactions

Ulipristal seems to be well tolerated. In a clinical study, headache was the most frequent adverse event, reported by 19.3 and 18.9 per cent of the ulipristal and levonorgestrel groups respectively.⁷

Rates of dysmenorrhoea (12.9 and 14.3 per cent with ulipristal and levonorgestrel respectively) and nausea (12.8 and 11.3 per cent respectively) were similar.⁷ Other common (occurring in 1/100 to <1/10) adverse events reported by women taking ulipristal include, according to the SPC, dizziness, mood disorders, pelvic pain and breast tenderness.

Furthermore, 74.6 per cent of women in the phase III studies had their next menstrual period within a week before and after the expected time. However, 6.8 per cent experienced menses more than seven days earlier than expected and 18.5 per cent had a delay of more than seven days. Menses was delayed for more than 20 days in 4 per cent who received ulipristal.

Pharmacists also need to be aware of potential drug-drug interactions. For example, cytochrome p450 3A4 meta-bolises ulipristal. The SPC advises against concomitant CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine and St John’s wort), which may reduce ulipristal concentrations. Using ulipristal with drugs that increase gastric pH (such as antacids, proton pump inhibitors and H2 receptor antagonists) may reduce absorption.⁴ However, according to the SPC, the relevance of this interaction for emergency contraception is not known.

To sum up, ulipristal offers women increased choice, widens the window of opportunity for emergency contraception and provides additional opportunities for pharmacists to advise about the wide range of regular contraceptives available.

References

1. The Lancet 2013; 382:1807-16
2. www.fpa.org.uk/contraception-help/your-guide-contraception
3. www.ema.europa.eu/docs/en_GB/ document_library/Press_release/2014/11/ WC500177649.pdf
4. www.fsrh.org/pdfs/ellaOneNewProduct Review1009.pdf
5. BMC Women’s Health 2014; 14:54
6. Human Reproduction Update 2005; 11:293-307
7. The Lancet 2010; 375:555-62