High potassium levels
Drospirenone is an antimineralocorticoid with potassium-sparing properties, though in most cases no increase of potassium levels is to be expected. In women with mild or moderate chronic kidney disease, or in combination with chronic daily use of other potassium-sparing medications (ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, heparin, antimineralocorticoids, or nonsteroidal anti-inflammatory drugs), a potassium level should be checked after two weeks of use to test for hyperkalemia. Persistent hyperkalemia that required discontinuation occurred in 2 out of around 1,000 women (0.2%) with 4 mg/day drospirenone alone in clinical trials. Blood clots
Birth control pills containing ethinylestradiol and a progestin are associated with an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence is about 4-fold higher on average than in women not taking a birth control pill. The absolute risk of VTE with ethinylestradiol-containing birth control pills is small, in the area of 3 to 10 out of 10,000 women per year, relative to 1 to 5 out of 10,000 women per year not taking a birth control pill. The risk of VTE during pregnancy is 5 to 20 in 10,000 women per year and during the postpartum period is 40 to 65 per 10,000 women per year. The higher risk of VTE with combined birth control pills is thought to be due to the ethinylestradiol component, as ethinylestradiol has estrogenic effects on liver synthesis of coagulation factors which result in a procoagulatory state.
In contrast to ethinylestradiol-containing birth control pills, neither progestogen-only birth control nor the combination of transdermal estradiol and an oral progestin in menopausal hormone therapy is associated with an increased risk of VTE.Different progestins in ethinylestradiol-containing birth control pills have been associated with different risks of VTE. Birth control pills containing progestins such as desogestrel, gestodene, drospirenone, and cyproterone acetate have been found to have 2- to 3-fold the risk of VTE of birth control pills containing levonorgestrel in retrospective cohort and nested case–control observational studies. However, this area of research is controversial, and confounding factors may have been present in these studies. Other observational studies, specifically prospective cohort and case control studies, have found no differences in risk between different progestins, including between birth control pills containing drospirenone and birth control pills containing levonorgestrel. These kinds of observational studies have certain advantages over the aforementioned types of studies, like better ability to control for confounding factors. Systematic reviews and meta-analyses of all of the data in the mid-to-late 2010s found that birth control pills containing cyproterone acetate, desogestrel, drospirenone, or gestodene overall were associated with a risk of VTE of about 1.3- to 2.0-fold compared to that of levonorgestrel-containing birth control pills.Androgenic progestins have been found to antagonize to some degree the effects of ethinylestradiol on coagulation. As a result, more androgenic progestins, like levonorgestrel and norethisterone, may oppose the procoagulatory effects of ethinylestradiol and result in a lower increase in risk of VTE.