The FDA has approved Quartette (Teva), an extended-cycle combination oral contraceptive containing increasing doses of the estrogen ethinyl estradiol (EE) combined with the progestin levonorgestrel (LNG). The rationale is that a gradual increase in the EE dose may reduce unscheduled bleeding or spotting, a common adverse effect of extended-cycle oral contraceptives.

The progestin levonorgestrel is available over the counter for emergency contraception as two 0.75-mg tablets taken 12 hours apart (generic formulations of Plan B) and as a single 1.5-mg tablet taken once (Plan B One-Step, and generics). A third emergency contraceptive, ulipristal (Ella – Watson), is available with a prescription.1 It appears that, pursuant to a court order, Plan B One-Step (but not the generic products), which was previously available over the counter from a pharmacist only for women 17 years and older, will now be available directly from pharmacy shelves with no age restrictions.

EMERGENCY CONTRACEPTION — Currently used hormonal methods of emergency contraception, which apparently mainly prevent or delay ovulation, can prevent 50-80% of pregnancies.2 They should be started as soon as possible within 72 hours after unprotected intercourse. One study found that taking levonorgestrel as late as 120 hours after unprotected intercourse could still be effective.3

Many oral contraceptives can be used in doses suitable for emergency contraception. All are recommended for use in 2 doses 12 hours apart, but given the effectiveness of a single dose of levonorgestrel 1.5 mg in Plan B One-Step, taking the tablets all at once might be an option. Patients who vomit within 1 hour of administration can repeat the dose. A copper IUD inserted within 5 days after intercourse can also provide emergency contraception.

ADVERSE EFFECTS — Nausea and vomiting occur less frequently with levonorgestrel alone than with estrogen-progestin combinations. Headache, abdominal pain and breast tenderness have been reported with either progestin-only or combination oral contraceptives. No fetal malformations caused by unsuccessful use of hormones for emergency contraception have been reported.

1. Ella: a new emergency contraceptive. Med Lett Drugs Ther 2011; 53:3.

2. DT Baird. Emergency contraception: how does it work? Reprod Biomed Online 2009; 18 suppl 1:32.

3. H von Hertzen et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet 2002; 360:1803.

Download complete U.S. English article

The FDA recently approved Skyla (Bayer), the first new intrauterine device (IUD) in the US in 12 years. It releases levonorgestrel, a synthetic progestin, over a period of 3 years. A table summarizing contraceptive methods available in the US appears on page 22.

The FDA has approved the use of ulipristal acetate (ella – Watson) as an emergency contraceptive that can be taken up to 5 days after unprotected intercourse. It is available only by prescription.

Six years after an FDA advisory committee recommended development of a combination tablet containing an oral contraceptive and folic acid,1 the FDA has approved Beyaz (Bayer), a combination of the oral contraceptive Yaz2 with 451 mcg of levomefolate calcium, the primary metabolite of folic acid.3 According to the FDA, an unpublished double-blind, randomized U.S. trial in 379 healthy women 18-40 years old found that the combination increased serum folate levels. In an unpublished German study using a similar oral contraceptive/ levomefolate combination (summarized in the package insert), folate levels remained elevated for several weeks after levomefolate was stopped.4

The standard US diet provides 50-500 mcg of absorbable folate per day, but the bioavailability of folate in mixed diets varies. Folic acid in supplements is more bioavailable than folate in food.5 Supplementing the diet of women of childbearing age with 400 mcg of folic acid per day, the amount contained in most multivitamin preparations, has dramatically decreased the incidence of neural tube defects in their offspring.To effectively prevent neural tube defects, folic acid supplementation should be started at least one month before conception and continued through the first 2-3 months of pregnancy. Since incorrect or inconsistent use of oral contraceptives may account for as many as one million pregnancies in the US each year, all women capable of becoming pregnant should take a folic acid supplement.6,7

1. Folic acid supplementation to prevent neural tube defects. Med Lett Drugs Ther 2004; 46:17.

2. Three new oral contraceptives. Med Lett Drugs Ther 2006; 48:77.

3. Choice of contraceptives. Treat Guidel Med Lett 2010; 8:89.

4. FDA approves combination contraceptive containing a folate. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227237.htm. Accessed October 5, 2010.

5. GP Oakley, Jr. Eat right and take a multivitamin. N Engl J Med 1998; 338:1060.

6. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 150:626.

7. AM Kaunitz. Oral contraceptive use, pregnancy intendedness and folic acid intake. FDA Advisory Committee for Reproductive Health Drugs meeting; December 15, 2003; Gaithersburg, MD. Available at http://www.fda.gov/ohrms/dockets/ac/03/transcripts/4002T1.DOC. Accessed November 3, 2010.

Download U.S. English

The FDA has approved the marketing of Natazia (Bayer), a 4-phase oral contraceptive containing the estrogen estradiol valerate and the progestin dienogest, both used for the first time in the US for this indication.

Combination oral contraceptives increase the risk of venous thromboembolism (VTE). Their benefits, in addition to preventing pregnancy, include lowering the risk of ovarian and endometrial cancer, reducing dysfunctional uterine bleeding and increasing serum hemoglobin concentrations. Are these benefits worth the risk? And are some combination oral contraceptives safer than others?

Transdermal, transvaginal and intrauterine hormone delivery systems have made highly effective contraceptive products more convenient to use. New oral contraceptive options include regimens with fewer or shorter hormone-free intervals.

In recent years, several new contraceptive options have become available in the United States. Novel hormone delivery systems such as transdermal, transvaginal and intrauterine devices have improved the convenience of highly effective contraceptive products. Like oral contraceptives and most barrier contraceptives, these devices do not protect against sexually transmitted diseases.

Seasonale (Barr), the first "extended-cycle" oral contraceptive, is now available in the US for pregnancy prevention. Active tablets containing 30 ╡g of ethinyl estradiol and 0.15 mg of levonorgestrel are taken for 84 consecutive days, followed by 7 days of inactive tablets, allowing for withdrawal bleeding only four times a year. Other combination oral contraceptives are dispensed as 21 days of active tablets and 7 days of placebo or no tablets, resulting in 13 withdrawal bleeding episodes each year.

An oral contraceptive (Yasmin - Berlex) containing 3 mg of drospirenone and 30 mcg of ethinyl estradiol is being promoted as having a low incidence of adverse effects.

A transdermal contraceptive patch (Ortho Evra — Ortho-McNeil) has been approved by the FDA. Each 20 cm² patch contains 6 mg of the progestin norelgestromin (the active metabolite of norgestimate) and 0.75 mg of ethinyl estradiol.

The FDA had approved an intrauterine contraceptive device that releases the synthetic progestin levonorgestrel over a period of five years. The device has been available in Europe for 10 years.

High doses of estrogens, with or without a progestin, have been used for many years to prevent pregnancy after unprotected coitus (Medical Letter, 31:93, 1989). Now the FDA has approved marketing of the Preven Emergency Contraceptive Kit (Gynetics, Inc.) for this indication. The kit, which will require a prescription, includes four tablets, each containing 50 g of ethinyl estradiol and 0.25 mg of levonorgestrel, and a pregnancy test to rule out a pre-existing pregnancy, which would be a contraindication to taking the hormones.