Drospirenone
Drospirenone is a spironolactone analogue with antiandrogenic and antimineralocorticoid activity, combined with ethinylestradiol in oral contraceptives such as Yaz and Yasmin. As Yaz, this combination is indicated for females of reproductive potential to prevent pregnancy, and also to treat the symptoms of premenstrual dysphoric disorder (PMDD) in women who choose an oral contraceptive as their method of contraception. Its effectiveness for PMDD has not been evaluated when used for more than three menstrual cycles.
Key points
- Drospirenone is broken down mainly by the liver enzyme CYP3A4, which carries out the 2-hydroxylation that is its major oxidative reaction.
- Taken by mouth, drospirenone reaches a bioavailability of between 76 and 85%.
- In clinical trials, 6.6% of 1,056 women stopped taking Yaz because of a side effect, most often headache or migraine (1.6%) and nausea or vomiting (1.0%).
How it works
Combined oral contraceptives prevent pregnancy mainly by suppressing ovulation, with the contraceptive effect also resting on changes in the endometrium, according to the Yasmin Summary of Product Characteristics. At clinically used doses, drospirenone also has antiandrogenic and mild antimineralocorticoid properties in addition to its progestogenic action. In clinical studies, the Pearl Index for method failure was 0.09, and the overall Pearl Index, covering both method and patient failure, was 0.57.
Safety specific to Drospirenone
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives, according to the FDA prescribing information for Yaz. This risk increases with age, particularly in women over 35, and with the number of cigarettes smoked, so women over 35 who smoke should not use Yaz.
Drospirenone itself has antimineralocorticoid activity, and Yaz’s 3 mg dose carries the potential for hyperkalaemia (raised blood potassium) in high-risk patients. Women on long-term daily medicines that can raise potassium should have their potassium levels checked during the first treatment cycle.
Any combined hormonal contraceptive raises the risk of venous thromboembolism (VTE, a blood clot) above that of women using none. For drospirenone-containing products, an estimated 9 to 12 in every 10,000 women develop a VTE in a year, according to the Yasmin Summary of Product Characteristics, and VTE may be fatal in 1 to 2% of cases. Yaz should be stopped if an arterial or venous thrombotic event occurs.