Drospirenone was patented in 1976 and introduced for medical use in 2000. It is available widely throughout the world. The medication is sometimes referred to as a "fourth-generation" progestin. It is available as a generic medication. In 2016 the version with ethinylestradiol was the 109th most prescribed medication in the United States with more than 6 million prescriptions.
Angeliq, a drospirenone and estradiol combination, has also been approved by the Food and Drug Administration (FDA) for treatment of moderate to severe vasomotor symptoms and/or vaginal atrophy associated with menopause.
The FDA has several approved indications for combined estrogen and drospirenone preparations. They are approved as a first-line therapy for menopausal symptoms such as the relief of hot flashes. Additionally, they have been shown to reduce the occurrence of bone fractures in postmenopausal women.
Drospirenone is sold as a combined birth control pill 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 released a pill based on Yasmin with the B vitamin folate (B9), which is marketed under the names Safyral and Beyaz. Worldwide it is also sold under the brand names Yaz and Yasminelle in a lower dosage containing drospirenone 3 mg/ethinylestradiol 20 μg. The drug is also available in combination with estradiol for use in menopausal hormone therapy. Drospirenone is not available on its own (i.e., as a standalone medication).
Yasmin/Jamine/Yarina contains 3 mg drospirenone and 30 μg 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 μg 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.
Yaz/Gianvi/Vestura contains 3 mg drospirenone and 20 μg ethinylestradiol per tablet. It is indicated for prevention of pregnancy as well as treatment of premenstrual dysphoric disorder for women who choose to use an oral contraceptive for contraception. There has also been evidence for this formulation to treat moderate acne for women 14 years of age or older who choose to use an oral contraceptive for birth control.
A complete list of FDA approved oral contraceptives containing drospirenone as of October 2012: Beyaz (Drospirenone 3 mg, ethinylestradiol 0.02 mg and levomefolate calcium 0.451 mg), Drospirenone and ethinylestradiol (Drospirenone 3 mg and ethinylestradiol 0.03 mg), Gianvi (Drospirenone 3 mg and ethinylestradiol 0.02 mg), Loryna (Drospirenone 3 mg and ethinylestradiol 0.02 mg), Ocella (Drospirenone 3 mg and ethinylestradiol 0.03 mg), Safyral (Drospirenone 3 mg, ethinylestradiol 0.03 mg, and levomefolate calcium 0.451 mg), Syeda (Drospirenone 3 mg and ethinylestradiol 0.03 mg), Yasmin (Drospirenone 3 mg and ethinylestradiol 0.03 mg), Zarah (Drospirenone 3 mg and ethinylestradiol 0.03 mg), Yaz (Drospirenone 3 mg and ethinylestradiol 0.02 mg)
While all oral contraceptives can increase the risk for venous thromboembolic events, including fatal blood clots, several studies have reported a greater risk for women taking contraceptives containing drospirenone. Women who take contraceptive pills containing drospirenone have a 6- to 7-fold 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. However, the absolute 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).
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 containing drospirenone for only 3 months or less and 290% higher for women taking drospirenone-containing oral contraceptives for 7 to 12 months, compared to women taking other types of oral contraceptives.
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 is an antagonist of the MR, the biological target of mineralocorticoids like aldosterone, and hence is an antimineralocorticoid. It has about 230% of the affinity of aldosterone and progesterone for the MR. Drospirenone is 8 to 10 times more potent as an antimineralocorticoid than spironolactone. As such, 3 mg drospirenone is equivalent to about 20 to 25 mg spironolactone in terms of antimineralocorticoid activity. The antimineralocorticoid activity exhibited by drospirenone promotes sodiumexcretion and decreases fluid retention. It has been said that the pharmacological profile of drospirenone more closely resembles that of progesterone than other progestins, because its antimineralocorticoid activity is a property that it uniquely shares with progesterone.
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.
Drospirenone was introduced for medical use in 2000. It is sometimes described as a "fourth-generation" progestin based on its time of introduction.
Society and culture
Drospirenone is the generic name of the drug and its INN, USAN, BAN, and JAN, while drospirénone is its DCF. Its name is a shortened form of the name 1,2-dihydrospirorenone or dihydrospirenone. Drospirenone is also known by its developmental code names SH-470 and ZK-30595 (alone), BAY 86-5300, BAY 98-7071, and SH-T-00186D (in combination with ethinylestradiol), and BAY 86-4891 (in combination with estradiol).
Drospirenone is marketed in combination with an estrogen under a variety of brand names throughout the world. Among others, it is marketed in combination with ethinylestradiol under the brand names Yasmin and Yaz and in combination with estradiol under the brand name Angeliq.
Drospirenone is marketed widely throughout the world.
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 US$402.6 million, for an average of US$212,000 per case, while setting aside US$610.5 million to settle the others.
As of July 17, 2015, there have been at least 4,000 lawsuits and claims still pending regarding venous thromboembolic events. This doesn't include the roughly 10,000 claims that Bayer has already settled without admitting liability. These claims of venous thromboembolic events have amounted to US$1.97 billion. Bayer also reached a settlement for arterial thromboembolic events, including stroke and heart attacks, for US$56.9 million.
Drospirenone (developmental code name LF-111) is or was under development by Leon Farma as a progestin-only pill for hormonal birth control in women, but as of March 2017 no recent reports of development have been identified. The formulation has reached phase IIIclinical trials for this indication.
Drospirenone (tentative brand name Estelle) is under development by Mithra Pharmaceuticals in combination with estetrol as a combined oral contraceptive for pregnancy in women. As of July 2018, it is in phase III clinical trials.
^ abcBayer (March 25, 2013). "Summary of Product Characteristics (SPC): Yasmin". London: electronic Medicines Compendium (eMC), Datapharm. Retrieved April 24, 2014. 4.3. Contraindications: • Severe chronic kidney disease or acute kidney failure. • Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
^ abBayer (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.
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