Elimination of drospirenone is virtually complete 10 days after the last dose. Chemistry
Drospirenone, also known as 1,2-dihydrospirorenone or as 17β-hydroxy-6β,7β:15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid, γ-lactone, is a synthetic steroidal 17α-spirolactone, or more simply a spirolactone. It is an analogue of other spirolactones like spironolactone, canrenone, and spirorenone. Drospirenone differs structurally from spironolactone only in that the C7α acetylthio substitution of spironolactone has been removed and two methylene groups have been substituted in at the C6β–7β and C15β–16β positions.Spirolactones like drospirenone and spironolactone are derivatives of progesterone, which likewise has progestogenic and antimineralocorticoid activity. The loss of the C7α acetylthio group of spironolactone, a compound with negligible progestogenic activity, appears to be involved in the restoration of progestogenic activity in drospirenone, as SC-5233, the analogue of spironolactone without a C7α substitution, has potent progestogenic activity similarly to drospirenone. History
Drospirenone was patented in 1976 and introduced for medical use in 2000. Schering AG of Germany has been granted several patents on the production of drospirenone, including WIPO and US patents, granted in 1998 and 2000, respectively. It was introduced for medical use in combination with ethinylestradiol as a combined birth control pill in 2000. Drospirenone is sometimes described as a "fourth-generation" progestin based on its time of introduction. The medication was approved for use in menopausal hormone therapy in combination with estradiol in 2005. Drospirenone was introduced for use as a progestogen-only birth control pill in 2019. A combined birth control pill containing estetrol and drospirenone was approved in 2021.
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 an agonist of the PR and an antagonist of the MR and AR, and hence is a progestogen, antimineralocorticoid, and antiandrogen. Drospirenone has no estrogenic activity and no appreciable glucocorticoid or antiglucocorticoid activity. Progestogenic activity
Drospirenone is an agonist of the PR, the biological target of progestogens like progesterone. It has about 35% of the affinity of promegestone for the PR and about 19 to 70% of the affinity of progesterone for the PR.