Drospirnone

Template:Drospirnone Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Drospirnone

Clinical data
Pregnancy category	US: X (Contraindicated)
Routes of administration	Oral
ATC code	G03AA12 (WHO) G03FA17 (WHO) (only combinations with estrogens)
Pharmacokinetic data
Bioavailability	76%
Protein binding	97%
Metabolism	Hepatic, minor (CYP3A4-mediated)
Elimination half-life	30 hours
Excretion	Renal and fecal
Identifiers
IUPAC name (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)- 1,3',4',6,6a,7,8,9,10,11,12,13,14,15,15a,16- hexadecahydro-10,13-dimethylspiro- [17H-dicyclopropa-6,7:15,16]cyclopenta [a]phenanthrene-17,2'(5H)-furan]-3,5'(2H)-dione)
CAS Number	67392-87-4 Y
PubChem CID	68873
DrugBank	DB01395 Y
ChemSpider	62105 Y
UNII	N295J34A25
KEGG	D03917 Y
ChEBI	CHEBI:50838 Y
ChEMBL	ChEMBL1509 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C24H30O3
Molar mass	366.493 g/mol
3D model (JSmol)	Interactive image
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
InChI InChI=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 Y Key:METQSPRSQINEEU-HXCATZOESA-N Y
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Overview

Drospirenone (INN, USAN), also known as 1,2-dihydrospirorenone, is synthetic, steroidal progestin with additional antimineralocorticoid and weak antiandrogen properties which is used as a hormonal contraceptive.

It is sold under the brand names Yasmin, Yasminelle, Yaz, Beyaz, Ocella, Zarah, and Angeliq, all of which are combination products 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, and for premenstrual dysphoric disorder. In combination with estradiol it is used to treat menopausal symptoms and premenstrual dysphoric disorder.

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.

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

The medication is contraindicated in people with 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 inhibitors, angiotensin-II receptor agonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDs.

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 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. 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.

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-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.

Pharmacokinetics

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.

Chemistry

It is an analog to spironolactone, with a molecular weight of 366.5 and the molecular formula C₂₄H₃₀O₃.

Formulations

The compound is part of certain newer oral contraceptive formulations:

• Yasmin 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.
• Yasminelle contains 3 mg drospirenone and 20 mcg ethinylestradiol per tablet and is used for contraception.
• Yaz and Beyaz contain 3 mg drospirenone and 20 mcg ethinylestradiol per tablet and is given for 24/4 days with the same indications.
• Ocella contains 3 mg drospirenone and 30 mcg ethinylestradiol per tablet and is taken daily.

It has also been formulated in medication to manage menopausal symptoms using 0.5 mg drsp and 1 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.
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.
• 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 CBC TV program Marketplace ran a segment discussing issues involved with the usage of Yaz/Yasmin

See also

• Progestin
• Combined oral contraceptive pill
• Oral contraceptive formulations
• Hormone replacement therapy
• Spironolactone

Further reading

• Krattenmacher R (2000). "Drospirenone: pharmacology and pharmacokinetics of a unique progestogen". Contraception. 62 (1): 29–38. doi:10.1016/S0010-7824(00)00133-5. PMID 11024226.

External links

• Yasmin product information
• Yaz product information
• Angeliq product information

Template:Progestogens