Clinicians change practice when it comes to EC

Your next patient is a young woman who has pressed for an appointment Monday morning after her boyfriend’s condom broke on Sunday night. Your formulary calls for use of progestin-only emergency contraception pills (ECPs). What is your next step?

Clinicians who prescribe progestin-only EC are moving to administering a single dose (1.5 mg) of the drug following research conducted by the Geneva-based World Health Organization (WHO) that indicates a single dose of levonorgestrel to be as effective in reducing the risk of pregnancy as two 0.75 mg doses taken 12 hours apart.1 A Nigerian study corroborated the finding that a single 1.5 mg dose of levonorgestrel is effective and safe.2

"There is a huge advantage in not having to take a second dose 12 hours later, simply because the regimen is simplified," says James Trussell, PhD, professor of economics and public affairs and director of the Office of Population Research at Princeton (NJ) University. He reviewed EC protocols during the recent Contraceptive Technology conference in Atlanta.3

The New York City-based Planned Parenthood Federation of America (PPFA) has now revised its medical standards and guidelines to include the new dosing option, according to Vanessa Cullins, MD, MPH, vice president of medical affairs.

"We give our clients a choice about which dosing option they want to use, and we point out the fact that new medical evidence shows that it is just as effective as the two-dosing option and has no more side effects than the other option," she says.

U.S. clinicians have one dedicated progestin-only product, Plan B. The drug is packaged with two 0.75 mg doses, and its package insert calls for the second dose to be taken 12 hours after the first dose. PPFA clinicians point out that the FDA labeling calls for the two doses when counseling on use of Plan B, says Cullins.

Barr Laboratories of Pomona, NY, has entered an agreement with the drug’s manufacturer, Washing-ton, DC-based Women’s Capital Corp. (WCC), to acquire Plan B, and Barr officials says they will continue to seek regulatory approval to take Plan B over the counter (OTC).

"As far as I know the focus now is entirely on Plan B OTC, not on any other label changes," says Trussell.

Labeling changes already have occurred in Europe. HRA Pharma of Paris has received regulatory approval to change its label to simplify the dosage and administration of its Norlevo EC product (levonorgestrel 0.75 mg tablet) from two 0.75 mg doses (one taken as soon as possible after unprotected intercourse and the other 12-24 hours later) to a single two-tablet intake of 1.5 mg.4 This change applies to the European Concerned Member States where the drug currently is marketed: as a behind-the-counter/over-the-counter product in France, Belgium, Luxembourg, Switzerland, Portugal, Sweden, Finland, Denmark, Norway; and as a prescription-only product in Spain, Italy, Greece, Netherlands, Germany (where it is marketed as Duofem), and Austria (where it is marketed as Vikela).

Further regulatory procedures soon will extend the label change to the more than 50 countries where Norlevo is available.4

"The application for the label change — single intake of the 2 x 0.75-mg tablet — has been filed in all the countries where Norlevo is on the market, and it is likely that the change will be approved in all the countries by early 2004," reports André Ulmann, MD, PhD, HRA Pharma spokesman.

A similar product, Levonelle, marketed by Schering AG, a Berlin-based pharmaceutical company, is scheduled to have its label revised this month to reflect the new single dosing, reports Trussell. Levonelle is marketed in Australia, Ireland, Italy, New Zealand, Portugal, Spain, and the United Kingdom.5

What is your approach when deciding when to administer EC? Research now indicates that ECPs (both levonorgestrel and Yuzpe regimen, marketed in the United States as Preven [Gynétics of Belle Mead, NJ]), can prevent pregnancy up to five days (120 hours) after unprotected intercourse.1,6,7

Results from the WHO study showed a significant trend toward lower efficacy the longer the delay between treatment and unprotected intercourse, and earlier WHO trials have indicated that pregnancy risk increases over time with delay of treatment,1,8 according to information provided by the International Consortium for Emergency Contraception, a 31-member global EC advocacy organization based in Washington, DC.

"These results underscore the importance of providing ECPs to women who seek treatment beyond 72 hours," according to the consortium.9 "To maximize the effectiveness of the method, however, women should be encouraged to take ECPs as soon as possible after unprotected intercourse."

References

1. Von Hertzen H, Piaggio G, Ding J, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: A WHO multicentre randomized trial. Lancet 2002; 360:1,803-1,810.

2. Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002; 66:269-273.

3. Trussell J. Emergency contraception: A cost-effective approach to preventing unintended pregnancy. Presented at the Contraceptive Technology: Quest for Excellence conference. Atlanta; October 2003.

4. Norlevo label evolves to reflect simpler, single-intake administration. Emergency Contraception Newsletter 2003. Accessed at www.cecinfo.org.

5. American Society for Emergency Contraception. Dedicated ECPs Worldwide. Updated Sept. 12, 2003. Accessed at www.emergencycontraception.org/asec/ecpillsworlwide.html.

6. Ellertson C, Evans M, Ferden S, et al. Extending the time limit for starting the Yuzpe regimen of emergency contraception to 120 hours. Obstet Gynecol 2003; 101:1,168-1,171.

7. Rodrigues I, Grou F, Joly J. Effectiveness of emergency contraceptive pills between 72 and 120 hours after unprotected sexual intercourse. Am J Obstet Gynecol 2001; 184:531-537.

8. Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352:428-433.

9. International Consortium for Emergency Contraception. Policy Statement. Regimen Update. July 2003. Accessed at: www.cecinfo.org/.

Resource

Review the International Consortium for Emergency Contraception’s policy statement on regimen update at its web site, www.cecinfo.org. Click on "Policy Statements" and "Regimen Update: Dosage and Timing;" the document is available in Adobe Portable Document Format.