|Systematic (IUPAC) name|
17-Hydroxy-6β,7β:15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid, γ-lactone
|Metabolism||Hepatic, minor (CYP3A4-mediated)|
|Biological half-life||30 hours|
|Excretion||Renal and fecal|
|ATC code||G03 G03 (only combinations with estrogens)|
|Molecular mass||366.493 g/mol|
|(what is this?)|
It is sold as a combined oral contraceptive under the brand names Yasmin (US, EU, Latin America), Jasmine (France), Yarina (Russia)  in a dosage containing drospirenone 3 mg/ethinylestradiol 30 µg. In the United States, Bayer Schering Pharma AG released a pill based on Yasmin with a B Vitamin folate (B9) and is marketed under the name Safyral.
Worldwide it is also sold under the brand names Yaz and Yasminelle in a lower dosage containing drospirenone 3 mg/ethinylestradiol 20 µg. In the United States, it is also marketed under the name Beyaz, carrying a B Vitamin folate with it.
Drospirenone is an ingredient in some birth control pills and hormone replacement therapy. In combination with ethinyl estradiol it is used as contraception, and for women who want contraception it is also approved by the U.S. Food and Drug Administration (FDA) to treat moderate acne and premenstrual dysphoric disorder.
Drospirenone is an aldosterone antagonist with potassium-sparing properties, though in most cases no increase of potassium levels is to be expected. In women with mild or moderate renal insufficiency, or in combination with chronic daily use of other potassium-sparing medications (ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, heparin, aldosterone antagonists, or NSAIDs), a potassium level should be checked after two weeks of use to test for hyperkalemia. In addition to contraindications common to all combined estrogen-progestin medications, drospirenone-containing medications are contraindicated in women with severe renal insufficiency according to European Medicines Agency (EMA)-approved labels, and contraindicated in women with renal insufficiency, adrenal insufficiency, or liver disease according to FDA-approved labels.
Women who take contraceptive pills containing drospirenone have a six- to sevenfold risk of developing thromboembolism (dangerous blood clots) compared to women who do not take any contraceptive pill, and have twice the risk (some epidemiological studies suggest thrice, according to the FDA) compared to women who take a contraceptive pill containing levonorgestrel, though the actual risk is small, in the neighborhood of 9 to 27 out of 10,000 women on an oral contraceptive for a year (up to 9 for levonorgestrel vs up to 27 for drospirenone, or about 0.09% vs 0.3% per year.)
While all oral contraceptives can increase the risk for venous thrombembolic events, including fatal blood clots, several studies have reported a greater risk for women taking contraceptives containing drospirenone. (Before becoming alarmed at the huge "relative" differences in risk, one must remember that the "actual" risks involved are quite small — in the neighborhood of 1 in 10,000 to 27 in 10,000 in a year).
When the U.S. Food and Drug Administration (FDA) became concerned about the risks of drospirenone, they funded studies based on the medical records of more than 800,000 women taking oral contraceptives. They found that the risk of VTE, which includes dangerous and potentially fatal blood clots, was 93% higher for women who had been taking oral contraceptives made with drospirenone for only 3 months or less and 290% higher for women taking drospirenone oral contraceptives for 7–12 months, compared to women taking other types of oral contraceptives. To determine the exact risk for women of different ages and different circumstances, further study is warranted.
The FDA recently updated the label for contraceptives containing drospirenone to include warnings for stopping use prior to and after surgery, and to warn that contraceptives with drospirenone may have a higher risk of dangerous blood clots.
Drospirenone binds strongly to the progesterone receptor (PR) and mineralocorticoid receptor (MR), with lower affinity, to the androgen receptor (AR), and very low affinity for the glucocorticoid receptor (GR). It is an agonist of the PR and an antagonist of the MR and AR, and hence, a progestogen, antimineralocorticoid, and antiandrogen. Drospirenone is said to be devoid of any estrogenic or glucocorticoid or antiglucocorticoid activity. It has potent antigonadotropic effects at sufficient dosages as a result of PR activation. It has been regarded that drospirenone has a pharmacological profile that is very closely related to that of natural progesterone, due to the combination of both progestogenic and antimineralocorticoid actions.
Drospirenone is 8–10 times more potent as an antimineralocorticoid relative to spironolactone (3 mg drospirenone is equivalent to about 20–25 mg spironolactone in this regard). It is more potent as an antiandrogen relative to spironolactone also but is less potent relative to cyproterone acetate, having about one-third the potency of this drug. Progestogenic, antimineralocorticoid, and mild antiandrogenic effects have been observed in humans during treatment with drospirenone at a dosage range of 0.5 to 4 mg per day orally.
The antimineralocorticoid properties exhibited by drospirenone promote sodium excretion and prevent water retention.
Drospirenone is taken orally with about 76% bioavailability. It is bound not by sex hormone-binding globulin or corticosteroid binding globulin, but by other serum proteins. Metabolites have not been shown to be biologically active, show up in urine and feces, and are essentially completely excreted within 10 days.
The compound is part of certain newer oral contraceptive formulations:
- Yasmin/Jamine/Yarina contains 3 mg drospirenone and 30 mcg ethinylestradiol per tablet. It is indicated for the prevention of pregnancy in women who elect an oral contraceptive.
- Safyral contains 3 mg drospirenone and 30 mcg ethinylestradiol per tablet. It is indicated for the prevention of pregnancy in women who elect an oral contraceptive as well as to provide a daily dose of folate supplementation, which is recommended for women in their reproductive years.� Folate lowers the risk of having rare neural tube birth defects in a pregnancy occurring during Safyral use or shortly after stopping.
In July 2012, Bayer notified its stockholders that there were more than 12,000 lawsuits against the company involving Yaz, Yasmin, and other oral contraceptives with drospirenone, and that the company by then settled 1,977 cases for $402.6 million, for an average of $212,000 per case, while setting aside $610.5 million to settle the others.
- Combined oral contraceptive pill
- Oral contraceptive formulations
- Hormone replacement therapy
- Buckingham, John, ed. (1994). "Spirorenone, INN S-01057". Dictionary of Natural Products, Volume 5, R–Z, R-00001 – Z-00072. London: Chapman & Hall. p. 5201. ISBN 0-412-46620-1. Retrieved May 28, 2012.
- Cerner Multum, Inc. (June 11, 2012). "drospirenone and ethinyl estradiol". Auckland, New Zealand: Drugs.com. Retrieved October 24, 2011.
- Bayer (March 25, 2013). "Summary of Product Characteristics (SPC): Yasmin". London: electronic Medicines Compendium (eMC), Datapharm. Retrieved April 24, 2014.
4.3. Contraindications: • Severe renal insufficiency or acute renal failure. • Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
- Nelson, Anita L.; Cwiak, Carrie (2011). "Combined oral contraceptives (COCs)". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. (eds.). Contraceptive Technology (20th revised ed.). New York: Ardent Media. pp. 249–341. ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734. pp. 287–288:
Health issues incorrectly attributed to modern COC use
9. Myth: Drospirenone-containing pills increase potassium levels in all women.
Drospirenone has antimineralocorticoid activity, which introduces the potential for hyperkalemia in high-risk patients; the 3 mg of drospirenone in these formulations has the same impact on electrolytes as 25 mg of spironolactone. The EURAS multinational study noted no increase in arrhythmias in users of drospirenone-containing COCs compared with other COC formulations.216 Use of these pills in combination with chronic daily use of ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, heparin, aldosterone antagonists, and NSAIDs may increase serum potassium. Note that intermittent use of NSAIDs does not pose any problems. If a woman is using other potassium-sparing drugs, test her potassium about 14 days after starting her first pack; if that value is normal, no further testing is needed for potassium.
- Bayer (April 10, 2012). "Yasmin full prescribing information" (PDF). Silver Spring, Md.: Food and Drug Administration (FDA). Retrieved April 14, 2012.
4. Contraindications: • Renal impairment. • Adrenal insufficiency. • Liver disease.
- Lidegaard, Øjvind; Milsom, Ian; Skovlund, Charlotte Wessel; Skjeldestad, Finn Egil; Løkkegaard, Ellen (October 25, 2011). "Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–9" (PDF). BMJ 343: d6423. doi:10.1136/bmj.d6423. PMC 3202015. PMID 22027398. Retrieved November 26, 2011.
- Lidegaard, Øjvind; Milsom, Ian; Geirsson, Reynir Tomas; Skjeldestad, Finn Egil (July 2012). "Hormonal contraception and venous thromboembolism" (PDF). Acta Obstetricia et Gynecologica Scandinavica 91 (7): 769–778. doi:10.1111/j.1600-0412.2012.01444.x. PMID 22568831. Retrieved October 22, 2012.
- Dunn, Nick (April 21, 2011). "The risk of deep venous thrombosis with oral contraceptives containing drospirenone. Data are inconclusive, but alternatives may be preferable unless specifically contraindicated. (editorial)" (PDF). BMJ 342: d2519. doi:10.1136/bmj.d2519. PMID 21511807. Retrieved April 25, 2011.
- Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E (1995). "Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity". Ann. N. Y. Acad. Sci. 761: 311–35. PMID 7625729.
- Fuhrmann, Ulrike; Krattenmacher, Rolf; Slater, Emily P.; Fritzemeier, Karl-Heinrich (1996). "The novel progestin drospirenone and its natural counterpart progesterone: Biochemical profile and antiandrogenic potential". Contraception 54 (4): 243–251. doi:10.1016/S0010-7824(96)00195-3. ISSN 0010-7824.
- Hermann P.G. Schneider; Frederick Naftolin (22 September 2004). Climacteric Medicine - Where Do We Go?: Proceedings of the 4th Workshop of the International Menopause Society. CRC Press. pp. 133–. ISBN 978-0-203-02496-6.
- Elger W, Beier S, Pollow K, Garfield R, Shi SQ, Hillisch A (2003). "Conception and pharmacodynamic profile of drospirenone". Steroids 68 (10-13): 891–905. PMID 14667981.
- Genazzani, Andrea R.; Mannella, Paolo; Simoncini, Tommaso (February 2007). "Drospirenone and its antialdosterone properties". Climateric 10 (Supplement 1): 11–18. doi:10.1080/13697130601114891. PMID 17364593. Retrieved November 26, 2011.
- "Yasmin/Safyral". Retrieved February 9, 2015.
- Johnson, Erica (January 20, 2011). "Video: Marketplace looks into alleged Yasmin risks". Marketplace (TV series). Vancouver, B.C.: CBC News. Retrieved October 13, 2011.
- Feeley, Jef; Kresge, Naomi (July 31, 2012). "Bayer's Yasmin lawsuit settlements rise to $402.6 million". Bloomberg News (New York). Retrieved November 11, 2012.
- Krattenmacher, Rolf (July 2000). "Drospirenone: pharmacology and pharmacokinetics of a unique progestogen". Contraception 62 (1): 29–38. doi:10.1016/S0010-7824(00)00133-5. PMID 11024226.