Drospirenone

from Wikipedia, the free encyclopedia
Structural formula
Structure of drospirenone
General
Non-proprietary name Drospirenone
other names

6 β , 7 β ; 15 β , 16 β -Dimethylen-3-oxo-17 α -pregn-4-ene-21,17-carbolactone

Molecular formula C 24 H 30 O 3
Brief description

white to almost white powder

External identifiers / databases
CAS number 67392-87-4
EC number 266-679-2
ECHA InfoCard 100.060.599
PubChem 68873
DrugBank DB01395
Wikidata Q419646
Drug information
ATC code
Drug class

Progestins

properties
Molar mass 366.49 g · mol -1
Physical state

firmly

Melting point

201.3 ° C

solubility

practically insoluble in water, slightly soluble in dichloromethane , soluble in acetone and methanol , slightly soluble in ethanol

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health

danger

H and P phrases H: 360
P: 201-308 + 313
Toxicological data

500–2000 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Drospirenone is a synthetically produced drug from the group of gestagens that was developed by Schering (now Bayer HealthCare ) and is contained as an effective component in " birth control pills " such as Yasmin .

In its pharmacological properties, drospirenone is very similar to the naturally occurring hormone progesterone due to a comparable receptor binding profile, and has anti-androgenic and anti- mineralocorticoid properties. Oral contraceptives (“birth control pills”) with drospirenone as a gestagenic component can be used to treat blemished skin ( acne ) due to their anti-androgenic effect and supposedly help to improve the appearance of the skin. The antimineral corticoid activity is said to prevent weight gain and other symptoms that are a result of fluid retention (e.g. breast tenderness).

Chemically, drospirenone is derived from the aldosterone antagonist spironolactone .

History

Wiechert and co-workers synthesized drospirenone at Schering AG as early as 1976. However, it took around 25 years until its pharmacological potential was recognized and the drug was brought onto the market in 2000.

Risk of thrombosis

In general, ovulation inhibitors (“birth control pills”) lead to a three to six-fold increased risk of thrombosis. Drospirenone is suspected of having an increased risk of thrombosis (compared to other ovulation inhibitors).

In epidemiological studies from Holland and Denmark from August 2009, an increased risk of thrombosis in connection with the active ingredient drospirenone was again reported. The risk increased with the age of the woman and the higher the estrogen content of the pill. These and other studies were used by the AkdÄ as an opportunity to present the current assessment of the risk of thromboembolic events under hormonal contraception and to provide information on the prescription. However, two studies published in 2010 came to the conclusion that drospirenone in birth control pills does not increase the risk of venous or arterial thrombosis more than the active ingredient levonorgestrel (older progestogen of the 2nd generation) and other older progestins. In February 2013, the European Medicines Agency initiated a risk assessment process for combined oral contraceptives containing drospirenone or other 3rd and 4th generation progestogens : This resulted in an annual risk of thrombosis of 5–7 / 10,000 women for combination contraceptives and 9–12 containing levonorgestrel / 10,000 women for drospirenone-containing women with a base rate of 2 / 10,000 women without hormone intake.

Perception in the media

In 2010, “Die Zeit” reported lawsuits brought against the pharmaceutical company Bayer HealthCare by patients who suffered thrombosis and embolism from drospirenone . According to “Die Zeit”, 1,750 lawsuits against Bayer HealthCare in the USA were known by April 2010, as well as several in Germany and Switzerland. In Austria, drospirenone was also discussed in the media. There are currently around 7,000 lawsuits pending against Bayer in the United States alone. At the end of May 2011 a German injured party filed a lawsuit against Bayer AG for the first time. In April 2012, Spiegel Online reported that Bayer would pay a total of around 142 million US dollars (107 million euros) to 651 affected women in a settlement. By September 2012, the amount of compensation in the USA had risen to 500 million euros. As of February 14, 2014, Bayer compensated over 8,250 women in the United States with a sum of 1.69 billion dollars, without taking any guilt into account.

On November 5, 2015, the Waldshut-Tiengen district court opened civil proceedings against Bayer. The student Felicitas Rohrer from Bad Säckingen is demanding damages and compensation for pain and suffering in the amount of 200,000 euros from the company due to damage to health allegedly caused by Yasminelle. At the time, plaintiff Rohrer's lawyer represented eight other women who see themselves harmed by Bayer contraceptive pills. In October 2018, the court advised a settlement in the case of Felicitas Rohrer, who claims to need anticoagulant medication after a deep vein thrombosis and pulmonary embolism, which prevented her from getting pregnant because of the complicated legal and medical issues . In December 2018 this lawsuit was dismissed.

Manufacturing

The multi-step, highly complex synthesis starts from 5-androsten-3 β -ol-17-one acetate.

Analytics

For the reliable qualitative and quantitative determination of drospirenone in physiological test material, the coupling of HPLC with mass spectrometry is used after adequate sample preparation .

Trade names

  • Combination with ethinylestradiol: aida (D), Aliane (A), Petibelle (D), Yasmin (D, A, CH, US), Yasminelle (D, A, CH), YAZ (D, A, CH, US), Yirala (A), Yiznell (...), as well as generics (D, A, CH)
  • Combination with estradiol: Angeliq (D, A, CH, US)

literature

  • R. Krattenmacher: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. In: Contraception. 62 (1), 2000, pp. 29-38. PMID 11024226
  • Freimut Leidenberger, Thomas Strowitzki, Olaf Ortmann: Clinical endocrinology for gynecologists. 5th edition. Springer , 2014, ISBN 978-3-642-38042-6 .

Web links

Individual evidence

  1. ↑ a b c data sheet DROSPIRENONE CRS (PDF) at EDQM , accessed on May 19, 2010.
  2. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 585.
  3. ↑ a b Datasheet Drospirenone, ≥98% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).
  4. ^ New drugs, 46 gynecological drugs, drospirenone. Pharmaceutical newspaper online, November 1, 2000, accessed November 10, 2015 .
  5. ↑ Drug Safety Mail 2010-096 of the Drug Commission of the German Medical Association with reference to an assessment by the European Medicines Agency (EMA).
  6. ↑ R. Wiechert, D. Bittler, U. Krebs, J. Casals-Stenzel, W. Losert, German Patent No. 2652761 (priority: 1976).
  7. ↑ a b N. Sehovic, KP Smith: Risk of venous thromboembolism with drospirenone in combined oral contraceptive products. In: Ann Pharmacother . 44, 2010, pp. 898-903. PMID 20371756 .
  8. ↑ a b Risk of venous thromboembolism when taking drospirenone-containing combined oral contraceptives (Yasmin ® / Yasminelle ® , Aida ® , Yaz ® , Petibelle ® ), 11.11.2011. Retrieved November 24, 2011 .
  9. ↑ Swissmedic confirms increased risk of embolism .
  10. ↑ J. Dinger, A. Assmann, S. Möhner, TD Minh: Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: results from a German case-control study. In: J Fam Plann Reprod Health Care. 36, 2010, pp. 123-129. PMID 20659364 .
  11. ↑ Combined hormonal contraceptives , February 7, 2013.
  12. ^ Lawsuits against Bayer. In: The time. No. 31, July 29, 2010.
  13. ↑ Sonja Niederbrunner: Drospirenone - a touch worse. (PDF) In: Echo Tirol. October 1, 2010, accessed January 11, 2012 .
  14. ↑ Countermotion to the BAYER Annual General Meeting on April 29, 2011
  15. ↑ Lawsuit filed against BAYER Group press release at cbgnetwork.org dated May 31, 2011.
  16. ↑ Nicola Kuhrt: Bayer pays 107 million euros to plaintiffs. In: Spiegel Online. April 27, 2012.
  17. ↑ Yasmin: “Do not put off injured parties any longer!” Press release at cbgnetwork.org from September 7, 2012.
  18. ↑ BASF Annual Report 2013, Section 32 "Legal Risks", accessed on June 28, 2016 at http://www.annualreport2013.bayer.com/en/legal-risks.aspx
  19. ↑ Yasminelle contraceptive pill: Damage claims against Bayer now also in Germany. In: Wirtschaftswoche. August 27, 2015.
  20. ↑ The court advises comparison in the controversy over the birth control pill . In: Spiegel Online . 19th October 2018.
  21. ↑ Lawsuit against Bayer dismissed for birth control pills In: zeit.de
  22. ↑ Bernd Schäfer: Natural substances of the chemical industry. 1st edition. Elsevier, 2007, ISBN 978-3-8274-1614-8 , pp. 361-362.
  23. ↑ N. Idota, M. Kobayashi, D. Miyamori, Y. Kakiuchi, H. Ikegaya: Drospirenone detected in postmortem blood of a young woman with pulmonary thromboembolism: A case report and review of the literature. In: Leg Med (Tokyo). 17 (2), Mar 2015, pp. 109–115. PMID 25454533 .
  24. ↑ C. Moser, D. Zoderer, G. Luef, M. Rauchenzauner, L. Wildt, A. Griesmacher, C. Seger: Simultaneous online SPE-LC-MS / MS quantification of six widely used synthetic progestins in human plasma. In: Anal. Bioanal. Chem. 403 (4), May 2012, pp. 961-972. PMID 22160205 .