New molecular entity: Drospirenone/ethinyl estradiol/levomefolate calcium (Beyaz) was approved to treat symptoms of premenstrual dysphoric disorder and moderate acne in women at least 14 years of age, and to supplement folate levels in women wishing to use oral contraception.
Drospirenone/ethinyl estradiol/levomefolate calcium is based upon the previously approved product Yaz (Bayer HealthCare Pharmaceuticals), but is a unique addition to the US market because it contains levomefolate calcium (a metabolite of the B-vitamin folic acid). Folate supplementation (at 0.4 mg daily) is recommended for all women of childbearing age in order to reduce the occurrence of neural tube defects such as spina bifida.
Efficacy. Data on drospirenone/ethinyl estradiol/levomefolate calcium's efficacy as an oral contraceptive and as a treatment of PMDD and acne are derived from Yaz clinical trials. Yaz has been found to be effective as an oral contraceptive, with a pregnancy rate (Pearl Index) of 1.41 (95% CI [0.73–2.47]) per 100 woman-years of use. Furthermore, Yaz was shown to result in statistically significantly greater improvement in Daily Record of Severity of Problems scores compared to placebo in women suffering from PMDD and improvement of symptoms in women suffering from moderate acne. The addition of levomefolate calcium to Yaz in randomized trials was shown to significantly increase folate levels in women.
Safety. The most frequent adverse reactions in contraception, acne, and folate clinical trials were headache/migraine, menstrual irregularities, nausea/vomiting, and breast pain/tenderness. The most frequent (>2% of participants) adverse reactions in PMDD clinical trials were: menstrual irregularities, nausea, headache, breast tenderness, fatigue, irritability, decreased libido, increased weight, and affect lability. Drospirenone/ethinyl estradiol/levomefolate calcium (and all combination oral contraceptives) increases the risks of venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, stroke), hepatic neoplasia, gallbladder disease, hypertension, ruptured ovarian cyst, and uterine leiomyoma. Consequently, drospirenone/ethinyl estradiol/levomefolate calcium should not be used in women with a high risk for these issues. The excess risk of thromboembolic events is highest during the first year of use. The risk also increases with age, particularly in women >35 years of age and with the number of cigarettes smoked. For this reason, drospirenone/ethinyl estradiol/levomefolate calcium should not be used by women who are >35 years of age and smoke. Drospirenone/ethinyl estradiol/levomefolate calcium should also be avoided in patients with renal impairment, adrenal insufficiency, or those predisposed to hyperkalemia, as drospirenone has antimineralcorticoid effects.