View source for Drospirnone

{{Drospirnone}}
{{CMG}} ;  '''Associate Editor(s)-in-Chief:''' [[User:Raviteja Reddy Guddeti|Raviteja Guddeti, M.B.B.S.]] [mailto:ravitheja.g@gmail.com] 


{{Drugbox| verifiedrevid = 443713428
| IUPAC_name = (6''R'',7''R'',8''R'',9''S'',10''R'',13''S'',14''S'',15''S'',16''S'',17''S'')-<br>1,3',4',6,6a,7,8,9,10,11,12,13,14,15,15a,16-<br>hexadecahydro-10,13-dimethylspiro-<br>[17''H''-dicyclopropa-6,7:15,16]cyclopenta<br>[a]phenanthrene-17,2'(5''H'')-furan]-3,5'(2''H'')-dione)
| image=Drospirenone.svg
| image2=Drospirenona3D.png
| CASNo_Ref = {{cascite|correct|CAS}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 62105
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = N295J34A25
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1509
| InChI = 1/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1
| smiles = O=C7O[C@@]6([C@@]3([C@H]([C@@H]2[C@@H]4[C@H](/C1=C/C(=O)CC[C@]1(C)[C@H]2CC3)C4)[C@@H]5C[C@@H]56)C)CC7
| InChIKey = METQSPRSQINEEU-HXCATZOEBK
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = METQSPRSQINEEU-HXCATZOESA-N
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number=67392-87-4
| ATC_prefix=G03
| ATC_suffix=AA12
| ATC_supplemental={{ATC|G03|FA17}} (only combinations with [[estrogen]]s)
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 50838
| PubChem=68873
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01395
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03917
| C = 24 | H = 30 | O = 3
| molecular_weight = 366.493 g/mol
| bioavailability= 76%
| metabolism = [[Liver|Hepatic]], minor ([[CYP3A4]]-mediated)
| elimination_half-life= 30 hours
| protein_bound = 97%
| excretion = [[Kidney|Renal]] and fecal
| pregnancy_US = X
| legal_status = 
| routes_of_administration= Oral
}}

==Overview==

'''Drospirenone''' ([[International Nonproprietary Name|INN]], [[United States Adopted Name|USAN]]), also known as '''1,2-dihydrospirorenone''', is [[synthetic]], [[steroid]]al [[progestin]] with additional [[antimineralocorticoid]] and weak [[antiandrogen]] properties which is used as a [[hormonal contraceptive]].<ref name="TammAyres1994">{{cite book | author1 = Ch Tamm | author2 = D. C. Ayres | author3 = R. A. Raphael | coauthors = M. Shamma | title = Dictionary of Natural Products | url = http://books.google.com/books?id=P4aNJh3pv2UC&pg=PA5201 | accessdate = 28 May 2012 | year = 1994 | publisher = CRC Press | isbn = 978-0-412-46620-5 | page = 5201}}</ref>

It is sold under the brand names '''Yasmin''', '''Yasminelle''', '''Yaz''', '''Beyaz''', '''Ocella''', '''Zarah''', and '''Angeliq''', all of which are [[combination product]]s of drospirenone with an [[estrogen]] such as [[ethinylestradiol]].

==Medical uses==
Drospirenone is part of some [[birth control pills]] and [[hormone replacement therapy]]. In combination with [[ethinyl estradiol]] it is used as [[contraception]], to treat moderate [[acne vulgaris|acne]], and for [[premenstrual dysphoric disorder]].<ref>http://www.drugs.com/mtm/drospirenone-and-ethinyl-estradiol.html</ref> In combination with [[estradiol]] it is used to treat [[menopause|menopausal symptoms]] and premenstrual dysphoric disorder.<ref>http://www.drugs.com/mtm/drospirenone-and-estradiol.html</ref>

==Adverse effects==
Women who take contraceptive pills containing drospirenone have a six- to sevenfold risk of developing [[thromboembolism]] compared to women who do not take any contraceptive pill, and twice the risk of women who take a contraceptive pill containing [[levonorgestrel]].<ref>{{cite journal | author = Lidegaard et al. | title = Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses | journal = BMJ | volume = 343 | pages = 1–15 | year = 2011 | doi= 10.1136/bmj.d6423 }}</ref>

Drospirenone can potentially cause [[hyperkalemia]] in high-risk patients, and is comparable to a 25&nbsp;mg dose of [[spironolactone]].

The medication is contraindicated in people with [[liver disease|hepatic dysfunction]], [[renal insufficiency]], [[adrenal insufficiency]], or in whom the use of oral contraceptives is contraindicated, such as smokers and patients with a history of [[DVT]], [[stroke]], or other blood clots. Because of the anti-mineralocorticoid effects care needs to be exercised when other drugs that may increase potassium levels are taken. Such medications include [[ACE inhibitor]]s, angiotensin-II receptor agonists, [[potassium-sparing diuretic]]s, potassium supplementation, [[heparin]], [[aldosterone antagonist]]s, and [[Non-steroidal anti-inflammatory drug|NSAID]]s.

Although there have been concerns raised regarding the safety of drospirenone containing oral contraceptives, the data is conflicting and it is unclear whether the increased risk of [[VTE|venous thrombembolic events]] seen in recent studies represents a true increase in this risk or whether flaws in the design of these studies are resulting in a false safety signal.  Further study in this regard appears to be warranted.<ref name=BMJ11>{{cite journal|last=Dunn|first=N|title=The risk of deep venous thrombosis with oral contraceptives containing drospirenone.|journal=BMJ (Clinical research ed.)|date=2011 Apr 21|volume=342|pages=d2519|pmid=21511807}}</ref>  However, the FDA recently updated the label for contraceptives containing drospirenone to include warnings for stopping use prior to and after surgery; moreover, the FDA acknowledges that contraceptives with drospirenone may be associated with a higher risk of venous thromboembolism.<ref>{{cite web|title=Highlights of Prescribing Information for Yasmin|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021098s022lbl.pdf|publisher=FDA}}</ref>

==Pharmacology==
===Pharmacodynamics===
Drospirenone differs from other synthetic [[progestins]] in that its pharmacological profile in preclinical studies shows it to be closer to the natural [[progesterone]]. As such it has potent [[antimineralocorticoid]] properties, counteracts the [[estrogen]]-stimulated activity of the [[renin-angiotensin system|renin-angiotensin]]-[[aldosterone]] system, and has also been shown to possess mild [[antiandrogen]] activity.

The antimineralocorticoid properties exhibited by drospirenone promote sodium excretion and prevent water retention.<ref>{{cite journal | author= Genazzani, Mannella & Simoncini | title= Drospirenone and its antialdosterone properties | journal: Climacteric | volume = 1 | pages = 11–18 | year = 2007 }}</ref>

===Pharmacokinetics===
Drospirenone is taken orally with about 76% [[bioavailability]]. It is bound not by [[sex hormone-binding globulin]] or [[Corticosteroid binding protein|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.

==Chemistry==
It is an [[analog (chemistry)| analog]] to [[spironolactone]], with a [[molecular weight]]  of 366.5 and the [[molecular formula]] C<sub>24</sub>H<sub>30</sub>O<sub>3</sub>.

==Formulations==
The compound is part of certain newer [[oral contraceptive formulations]]:
* Yasmin contains 3&nbsp;mg drospirenone and 30&nbsp;mcg [[ethinylestradiol]] per tablet. It is indicated for the prevention of pregnancy in women who elect an oral contraceptive.
* Yasminelle contains 3&nbsp;mg drospirenone and 20&nbsp;mcg ethinylestradiol per tablet and is used for contraception.
* Yaz and [[Beyaz (drug)|Beyaz]] contain 3&nbsp;mg drospirenone and 20&nbsp;mcg ethinylestradiol per tablet and is given for 24/4 days with the same indications.
* Ocella contains 3&nbsp;mg drospirenone and 30&nbsp;mcg ethinylestradiol per tablet and is taken daily.
It has also been formulated in medication to manage [[menopause|menopausal]] symptoms using {{nowrap|0.5 mg drsp}} and 1&nbsp;mg [[estradiol]] per day by oral application. This medication was introduced in the United States in 2007 as Angeliq.

==Litigation ==
In 2008, a series of television commercials prompted the FDA to cite Bayer for overstating the approved uses of Yaz while failing to adequately address the risks of the drug.  Bayer was required to dispel the inaccurate information contained in those ads by creating new ads that clarified the drug's approved uses.<ref name="courthousenews.com">http://www.courthousenews.com/2009/10/15/Yasmin_YAZ_Claims_Against_Bayer_Mount_Up.htm</ref><br />
On October 8, 2009, Bayer disclosed that 129 lawsuits had been brought against them over the side effects and marketing of Yaz and Yasmin. The allegations include (but are not limited to):
* Glossing over risks associated with the products and overstating their approved uses in an effort to mislead users of Yaz and Yasmin into believing that the drugs were safe.<ref name="courthousenews.com"/><ref name="Reuters Press Release">{{cite news| url=http://www.reuters.com/article/pressRelease/idUS204695+21-Oct-2009+BW20091021 | work=Reuters | title=Nurse Charges Dangerous Yaz Birth Control Drug "Altered My Life" | date=October 21, 2009}}</ref>
* Failure to properly research the medication.
* Failing to recall the drug after post-marketing reports demonstrated that the risk of potentially life-threatening side effects of Yasmin and Yaz outweighed potential benefits that could be achieved via other available oral contraceptives.

In September 2009, the FDA cited Bayer for sending out potentially low-quality batches of drosperinone.  Bayer justified the shipments by explaining that they monitor the "average" quality of all shipments, not the quality of each individual batch.

In October 2011 the [[Canadian Broadcasting Corporation|CBC]] TV program ''[[Marketplace_(TV_series)|Marketplace]]'' ran a segment discussing issues involved with the usage of Yaz/Yasmin
<ref>{{cite news| url=http://www.cbc.ca/news/health/story/2011/01/20/yasmin-marketplace.html | work=CBC News | title=VIDEO: Marketplace looks into alleged Yasmin risks | date=January 20, 2011}}</ref>

==See also==
* [[Progestin]]
* [[Combined oral contraceptive pill]]
* [[Oral contraceptive formulations]]
* [[Hormone replacement therapy (menopause)|Hormone replacement therapy]]
* [[Spironolactone]]

==References==
{{Reflist}}

==Further reading==
* {{cite journal | author = Krattenmacher R | title = Drospirenone: pharmacology and pharmacokinetics of a unique progestogen | journal = Contraception | volume = 62 | issue = 1 | pages = 29–38 | year = 2000 | pmid = 11024226 | doi = 10.1016/S0010-7824(00)00133-5}}

==External links==
* [http://www.yasmin-us.com/ Yasmin product information]
* [http://www.yaz-us.com Yaz product information]
* [http://www.angeliq.com/html/ Angeliq product information]


{{Progestogens}}
{{Androgenics}}
{{Mineralocorticoids}}
{{Progestogenics}}

[[Category:Cyclopropanes]]
[[Category:Enantiopure drugs]]
[[Category:Lactones]]
[[Category:Progestogens]]
[[Category:Spiro compounds]]

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