Berlex' Yaz

The FDA approved Berlex'Yaz (drospirenone/ethinyl estradiol) as an oral contraceptive (OC) in March 2006. It is a monophasic OC that contains 3 mg of drospirenone and 0.02 mg of ethinyl estradiol. The course of therapy differs from usual OCs in that there are 24 active pill days and 4 placebo days, as opposed to the usual 21/7 regimen. Studies have shown that by shortening the hormone-free interval the symptoms associated with hormone withdrawal may be reduced. This regimen helps improve adherence and continuation of the OC.¹

Pharmacodynamics

Drospirenone and ethinyl estradiol act by suppressing gonadotropins. This mechanism primarily inhibits ovulation. It also, however, promotes changes in cervical mucus and thickens the endometrium, increasing the difficulty of sperm to enter the uterus and reducing the likelihood of implantation.

Drospirenone is a spironolactone analogue with antimineralocorticoid activity. It has no androgenic, glucocorticoid, estrogenic, or antiglucocorticoid activity. It has been shown to have antiandrogenic activity.²

Clinical Trial as an OC

The contraceptive efficacy, bleeding profile, and safety of Yaz were assessed in a multicenter, international, openlabel, noncomparative study. The researchers enrolled 1027 healthy women aged 17 to 36 years old requesting contraception for being at risk of pregnancy. Due to missing start and stop dates, the treatment exposure could not be calculated for 9 participants. Therefore a total of 1018 women completed 11,140 treatment cycles in which backup contraception was not used.³

During the course of the study, 11 pregnancies occurred, 6 of them due to patient nonadherence. According to Kaplan-Meier life-table analysis, the cumulative 1-year pregnancy rate was 1.26% (95% confidence interval, 0.52- 2.01). This rate corresponds with contraception protection of 99%.^2,3

Because of adverse events, protocol deviation, withdrawal of consent, loss of follow-up, nonadherence, pregnancy, and unspecified reasons, 35.4% (n = 371) of the 1027 discontinued the study prematurely.³

Clinical Trial for PMDD

Berlex announced in October 2006 that the FDA had approved Yaz for the treatment of the emotional and physical symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an OC as their method of contraception.⁴ In a multicenter, double-blind, placebo-controlled, randomized trial, 449 women aged 18 to 40 years old who had been diagnosed with PMDD were studied. They received either Yaz (n = 231) or placebo (n = 218) for 3 treatment cycles, following a 2-menstrual cycle qualification period. Obtained from these qualification and treatment cycles, the primary outcome measure was the difference in daily record of severity of problems (DRSP) scores.

The mean total DRSP score decreased by 47% in the Yaz group (from 77.40 + 16.7 to 41.2 + 17.3), compared with 38% in the placebo group (from 78.1 + 17.8 to 48.1 + 21.1) during the qualification cycles. Over the 3 treatment cycles, the adjusted mean difference between the DRSP score in the Yaz group (-37.49) and the placebo group was significant (7.50; P = .001). The investigators found Yaz to be more effective in treating symptoms of PMDD versus placebo.⁵

Safety

Because drospirenone has antimineralocorticoid activity, it has the potential risk of causing hyperkalemia in high-risk patients comparable to that of a 25-mg dose of spironolactone. Yaz should not be used by women with renal or adrenal insufficiency or hepatic dysfunction. Women who take medications that elevate serum potassium levels (angiotensin- converting enzyme inhibitors and angiotensin-II receptor blockers, potassium- sparing diuretics, heparin, nonsteroidal anti-inflammatory drugs, and aldosterone antagonists) should have their potassium levels checked during the first treatment cycle.⁶

The most common side effects are nausea, vomiting, bleeding between menstrual periods, weight gain, and breast tenderness.

As with all OCs, Yaz does not protect against HIV and other sexually transmitted diseases.

Cigarette smoking increases the risk of serious cardiovascular events. Women who use Yaz should be strongly advised not to smoke.

Ms. Domenici and Dr. Patel are both pharmacists at Brigham and Women's Hospital, Boston, Mass.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Rybovic, Pharmacy Times, Ascend Media Healthcare, 103 College Road East, Princeton, NJ 08540; or send an email request to: arybovic@ascendmedia.com.