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Estradiol valerate, dienogest OC gets nod
Add Natazia, an estradiol valerate/dienogest pill, to the list of oral contraceptives approved by the Food and Drug Administration (FDA) and now available to U.S. women. The drug, marketed by Bayer HealthCare Pharmaceuticals of Wayne, NJ, is now available in pharmacies nationwide and is competitively priced with other branded oral contraceptive products, says Rose Talarico, company spokesperson. [Contraceptive Technology Update checked drug availability/pricing at four Atlanta pharmacies. Two pharmacies (Walgreens and Target) stocked the drug at $86.99 and $89.99 respectively, while two others (Publix and Kroger) had not yet added the formulation.]
The pill contains estradiol valerate and dienogest, formulated in a 4-phasic regimen. Estradiol valerate is a synthetic estrogen that is converted to estradiol in a woman's body. Dienogest is one of several new progestins such as drospirenone, Nestorone, nomegestrol acetate, and trimegestone that have been synthesized in the last two decades. These new progestins are formulated to have no androgenic or estrogenic actions and to be closer in activity to the physiological hormone progesterone.1
The use of natural estradiol (E2) has been studied.2 The site of metabolism of estradiol valerate to E2 occurs during absorption, so what the liver "sees" and what appears in her circulation is E2, says Anita Nelson, MD, medical director of the women's health care programs at Harbor-UCLA Medical Center in Torrance, CA.
Researchers evaluated the safety and efficacy of Natazia in two multicenter Phase 3 clinical trials in North America and Europe. Results of both trials, which involved 1,867 women, indicate the formulation to be effective as a hormonal contraceptive.
The study conducted in the United States and Canada was a multicenter, open-label, single-arm, unintended pregnancy study. It included 490 women ages 18-35 who were treated for up to 28 cycles of 28 days each. Weight range for treated women was 40 to 100 kg (mean weight: 62.5 kg) and the body mass index (BMI) range was 14-30 kg/m2 (mean BMI: 23.3 kg/m2). Of the treated women, 15% discontinued the study treatment due to an adverse event, 13% were lost to follow up, 10% withdrew their consent, 8% discontinued due to other reason, 1% discontinued due to protocol deviation, and 1% discontinued due to pregnancy.
The study conducted in Europe (Germany, Austria, and Spain) was a multicenter, open-label, single-arm contraceptive reliability study, with a total of 1,377 healthy subjects treated for 20 cycles of 28 days each. The weight range for treated women in the European study was 38-98 kg (mean weight: 63.8 kg) and the BMI range was 15-31.8 kg/m2 (mean BMI: 22.8 kg/m2). Of treated women, 10% discontinued the study treatment due to an adverse event, 5% discontinued due to other reason, 2% were lost to follow up, 2% discontinued due to protocol deviation, 2% withdrew their consent, and 1% discontinued due to pregnancy.3
The Pearl Index (PI) was the primary measure for assessing contraceptive reliability; the PI calculation was based on criteria established by FDA (pregnancies that occurred in women age 18-35 years during cycles 1 to 13 including pregnancies seven days post-treatment). In the North American study, five pregnancies occurred over 3,969 exposure cycles (PI = 1.64; failure rate at the end of year one was 0.016). A total of nine pregnancies occurred over 11,275 exposure cycles in the European trial (PI = 1.04; failure rate at the end of year 1 was 0.010).3
As with any oral contraceptive, women should be counseled on potential side effects. The most common treatment-emergent adverse reactions (≥2%) in Natazia's clinical trials were: headache (including migraines) (13.2%); metrorrhagia and irregular menstruation (8.0%); breast pain, discomfort, or tenderness (6.6%); nausea or vomiting (6.5%); acne (3.9%); and increased weight (2.8%).3
How to take Natazia's tablets
Natazia's tablets must be taken at the same time every day in the order directed on the blister pack. The daily dose should not be skipped or delayed by more than 12 hours. After taking the last white pill (day 28) of the blister pack, women should be instructed to start taking the first dark yellow pill from a new blister pack the very next day whether or not she is having her period. Be sure to counsel for women to have a back-up method such as condoms or spermicides on hand in case pills are missed. Whether or not a woman is switching from another form of hormonal birth control or a non-hormonal method, she should be counseled to use a non-hormonal back-up method such as condoms or spermicide for the first nine days of initial Natazia use.
Natazia carries the same contraindications as ethinyl estradiol pills. It should not be used in women with a high risk of arterial or venous thrombotic diseases, undiagnosed abnormal genital bleeding, breast cancer or other estrogen- or progestin-sensitive cancer, liver tumors (benign or malignant) or liver disease, or who are pregnant.