drospirenone and cyproterone acetate. In the early 2010s, the FDA updated the label for birth control pills containing drospirenone and other progestins to include warnings for stopping use prior to and after surgery, and to warn that such birth control pills may have a higher risk of blood clots. Breast cancer Drospirenone has been found to stimulate the proliferation and migration of breast cancer cells in preclinical research, similarly to certain other progestins. However, some evidence suggests that drospirenone may do this more weakly than certain other progestins, like medroxyprogesterone acetate. The combination of estradiol and drospirenone has been found to increase breast density, an established risk factor for breast cancer, in postmenopausal women. Data on risk of breast cancer in women with newer progestins like drospirenone are lacking at present. Progestogen-only birth control is not generally associated with a higher risk of breast cancer. Conversely, combined birth control and menopausal hormone therapy with an estrogen and a progestogen are associated with higher risks of breast cancer. Overdose These have been no reports of serious adverse effects with overdose of drospirenone. Symptoms that may occur in the event of an overdose may include nausea, vomiting, and vaginal bleeding. There is no antidote for overdose of drospirenone and treatment of overdose should be based on symptoms. Since drospirenone has antimineralocorticoid activity, levels of potassium and sodium should be measured and signs of metabolic acidosis should be monitored. Interactions Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may influence the levels and efficacy of drospirenone. Treatment for 10 days with 200 mg twice daily ketoconazole, a strong CYP3A4 inhibitor among other actions, has been found to result in a moderate 2.0- to 2.7-fold increase in exposure to drospirenone. Drospirenone does not appear to influence the metabolism of omeprazole (metabolized via CYP2C19), simvastatin (metabolized via CYP3A4), or midazolam (metabolized via CYP3A4), and likely does not influence the metabolism of other medications that are metabolized via these pathways. Drospirenone may interact with potassium-sparing medications such as ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, potassium supplements, heparin, antimineralocorticoids, and nonsteroidal anti-inflammatory drugs to further increase potassium levels. This may increase the risk of hyperkalemia (high potassium levels). Pharmacology Pharmacodynamics Drospirenone binds with high affinity to the progesterone receptor (PR) and mineralocorticoid receptor (MR), with lower affinity to the androgen receptor (AR), and with very low affinity to the glucocorticoid receptor (GR). It is