Premarin

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Premarin
Combination of
Estrone sulfate Estrogen
Equilin Estrogen
Equilenin Estrogen
Clinical data
AHFS/Drugs.com Consumer Drug Information
Pregnancy
category
  • X
Legal status
  • (Prescription only)
Routes of
administration
Oral, topical, IV
Identifiers
CAS Registry Number 12126-59-9 YesY
ATC code G03CA57
PubChem CID: 656613
ChemSpider 570974 YesY
UNII IU5QR144QX YesY
 YesY (what is this?)  (verify)

Premarin is the commercial name for a medication consisting primarily of conjugated estrogens. Isolated from mares' urine (pregnant mares' urine), it is manufactured by Wyeth Pharmaceuticals (part of Pfizer since January 2009) and has been marketed since 1942. It is available in oral (0.3/​0.45/​0.625/​0.9/​1.25 mg), IV, and topical (vaginal) form.[1]

Medical uses[edit]

Premarin is a form of hormone replacement therapy.[2] Premarin pills are used most commonly in post menopausal women who have had a hysterectomy to treat hot flashes, and burning, itching, and dryness of the vagina and surrounding areas.[3] It can also be used in conjunction with a progestin pill in women who have not had a hysterectomy. For women already taking the drug it can be used to treat osteoporosis, although it is not recommended solely for this use.[4] Some lesser known uses are the treatment of breast cancer in both men and women and the treatment of prostate cancer in men.[5][6]

Side effects[edit]

The most common side effects associated with Premarin use are vaginal yeast infections, vaginal spotting or bleeding, painful menses, and cramping of the legs.While there are some contradictory data, estrogen alone does not appear to increase the risk of coronary heart disease or breast cancer, like estrogen with progestin does. [7]

Pharmacology[edit]

The major forms of estrogen in Premarin are estrone (>50%), equilin (15-25%) and equilenin. The estrogens in Premarin are often called "conjugated equine estrogens" (CEE) because the estrogen molecules are generally present with hydrophilic side-groups attached such as sulfate.[8] Thus, estrone sulfate is actually the major active constituent in Premarin. Estrone sulfate is easily absorbed into the blood after the tablets are taken by women.[9]

Society and culture[edit]

History[edit]

Premarin was first introduced in 1942 by Wyeth Ayerst as a treatment for hot flashes and other symptoms of menopause; at that time, Wyeth Ayerst only had to prove its safety, and not its efficacy.[10] In response to the 1962 Kefauver Harris Amendment the FDA had its efficacy reviewed, and in 1972 found it effective for menopausal symptoms and probably effective for osteoporosis.[11] The review also determined that two estrogens—estrone sulfate and equilin sulfate—were primarily responsible for Premarin’s activity, and it laid the groundwork for Abbreviated New Drug Application (ANDA) submissions of generic versions.[10] In 1984 an NIH consensus panel found that estogens were effective for preventing osteoporosis[12] and 1986 the FDA announced in the Federal Register that Premarin was effective for preventing osteoporosis.[13] This announcement led to a rapid growth in sales, and interest from generic manufacturers to introduce generic versions.[10]

Health effects[edit]

Research starting in 1975 showed substantially increased risk of endometrial cancer.[14][15] Since 1976 the drug has carried a label warning about the risk.[16] As part of the Women's Health Initiative sponsored by the National Institutes of Health, a large-scale clinical trial for Hormone Replacement Therapy showed that long-term use of progestin and estrogen may increase the risk of strokes, heart attacks, blood clots, and breast cancer.[17] Following these results, Wyeth experienced a significant decline in its sales of Premarin, Prempro (conjugated equine estrogens) and related hormones, from over $2 billion in 2002 to just over $1 billion in 2006.[18]

Litigation[edit]

This drug has been the subject of litigation; more than 13,000 people have sued Wyeth between 2002 and 2009. Wyeth and Pharmacia & Upjohn prevailed in the vast majority of hormone therapy cases previously set for trial through a combination of rulings by judges, verdicts by juries, and dismissals by plaintiffs themselves.[19] Of the company’s losses, two of the jury verdicts were reversed post-trial and others are being challenged on appeal. Wyeth also won five summary judgments on Prempro cases and had 15 cases voluntarily dismissed by plaintiffs. The company won dismissals in another 3,000 cases.[20] In 2006, Mary Daniel, in a trial in Philadelphia, was awarded $1.5 million in compensatory damages as well as undisclosed punitive damages. As of 2010, Wyeth had won the last four of five cases, most recently in Virginia, finding that they were not responsible for the breast cancer of plaintiff Georgia Torkie-Tork.[21] Wyeth has been quoted as saying "many risk factors associated with breast cancer have been identified, but science cannot establish what role any particular risk factor or combination play in any individual woman's breast cancer." [22] Wyeth's counsel in the case also noted that in the WHI trial, 99.62 percent of women took the drug and "did not get breast cancer."[20]

Controversy[edit]

Animal welfare groups claim that animal husbandry and urine collection methods used in Premarin's production cause undue stress and suffering to the mares involved. Allegations of abuse range from concern over stall size, access to water, exercise, cruel treatment, collection system, continuous breeding cycles, and premature death.[23]

See also[edit]

References[edit]

  1. ^ Premarin (conjugated estrogens) Vaginal cream - detailed view: safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER) November 2008
  2. ^ Greer, Iain A.; Ginsberg, Jeff; Forbes, Charles (29 December 2006). Women's vascular health. CRC Press. ISBN 9780340809976. 
  3. ^ Nezhat, Camran; Nezhat, Farr; Nezhat, Ceana (7 July 2008). Nezhat's Operative gynecologic laparoscopy and hysteroscopy. Cambridge University Press. ISBN 9781139472005. Retrieved 7 May 2015. 
  4. ^ Maeda, Sergio Setsuo; Lazaretti-Castro, Marise; Maeda, Sergio Setsuo; Lazaretti-Castro, Marise (2014). "An overview on the treatment of postmenopausal osteoporosis". Arquivos Brasileiros de Endocrinologia & Metabologia 58 (2): 162–171. doi:10.1590/0004-2730000003039. ISSN 0004-2730. Retrieved 2015-05-07. 
  5. ^ "Breast cancer: major risk factors and recent developments in treatment". Asian Pac J Cancer Prev 15 (8): 3353–8. 2014. PMID 24870721. 
  6. ^ Learning, Jones & Bartlett (2015-01-14). 2015 Nurse's Drug Handbook. Jones & Bartlett Publishers. ISBN 9781284091373. Retrieved 2015-05-07. 
  7. ^ http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm121062.htm
  8. ^ Bernstein, S.; Solomon, S. (2012-12-06). Chemical and Biological Aspects of Steroid Conjugation. Springer Science & Business Media. ISBN 9783642951770. Retrieved 2015-05-07. 
  9. ^ Troy, David B.; Beringer, Paul (2006). Remington: The Science and Practice of Pharmacy. Lippincott Williams & Wilkins. ISBN 9780781746731. Retrieved 2015-05-12. 
  10. ^ a b c Jim Kling October 2000 The Strange Case of Premarin Modern Drug Discovery (3):8 46–52
  11. ^ Federal Register 37, July 25, 1972 pp 14826-28
  12. ^ National Institutes of Health Consensus Development Conference Statement. April 2-4, 1984 Osteoporosis
  13. ^ Food and Drug Administration. May 5, 1997 Conjugated Estrogens - Letter from Dr. Janet Woodcock: Approvability of a Synthetic Generic Version of Premarin
  14. ^ Ziel HK, Finkle WD (4 December 1975). "Increased risk of endometrial carcinoma among users of conjugated estrogens". New England Journal of Medicine 293: 1167–1170. doi:10.1056/NEJM197512042932303. PMID 171569. 
  15. ^ McDonald TW et al. (15 March 1977). "Exogenous estrogen and endometrial carcinoma: case-control and incidence study". American J Obstet Gynecol 127: 572–580. PMID 190887. 
  16. ^ Natasha Singer and Duff Wilson (12 December 2009). "Menopause, as Brought to You by Big Pharma". New York Times. 
  17. ^ Brunner RL et al; Womens Health Initiative Investigators (26 September 2005). "Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative randomized clinical trial". Archives of Internal Medicine 165 (17): 1976–1986. doi:10.1001/archinte.165.17.1976. PMID 16186467. 
  18. ^ "Earnings Results for the 2006 Fourth Quarter and Full Year" (PDF) (Press release). Wyeth. 
  19. ^ "Pfizer Statement on Prempro". Indy News Channel. [dead link]
  20. ^ a b Jef Feeley (February 24, 2010). "Pfizer wins trial over claim Prempro caused cancer". Bloomberg. 
  21. ^ "Pfizer properly warned about Prempro risks, jury finds". 3 December 2010. 
  22. ^ "Legal Intelligencer: Philadelphia jury returns defense verdict in HRT case, Amaris Elliott Engel". 
  23. ^ The HRT horses (NBC)

External links[edit]