Norelgestromin

Overview

Norelgestromin, or norelgestromine, sold under the brand names Evra and Ortho Evra among others, is a progestin medication which is used as a method of birth control for women. The medication is available in combination with an estrogen and is not available alone. It is used as a patch that is applied to the skin.[1][2][3] WP

Side effects of the combination of an estrogen and norelgestromin include menstrual irregularities, headaches, nausea, abdominal pain, breast tenderness, mood changes, and others. Norelgestromin is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has very weak androgenic activity and no other important hormonal activity.[4][5][6] WP

Norelgestromin was introduced for medical use in 2002. It is sometimes referred to as a "third-generation" progestin. Norelgestromin is marketed widely throughout the world. It is available as a generic medication.[1][7–10] WP

Uses, dosage and effects

Medical uses

Norelgestromin is used in combination with ethinyl estradiol in contraceptive patches. These patches mediate their contraceptive effects by suppressing gonadotropin levels as well as by causing changes in the cervical mucus and endometrium that diminish the likelihood of pregnancy.[2][3][4] WP

Available forms

Norelgestromin is available only as a transdermal contraceptive patch in combination with ethinyl estradiol. The Ortho Evra patch is a 20 cm², once-weekly adhesive that contains 6.0 mg norelgestromin and 0.6 mg ethinyl estradiol and delivers 200 μg/day norelgestromin and 35 μg/day ethinyl estradiol.[2][4][11] WP

Risks and side effects

Side effects

Norelgestromin has mostly been studied in combination with an estrogen, so the side effects of norelgestromin specifically or on its own have not been well-defined. Side effects associated with the combination of ethinylestradiol and norelgestromin as a transdermal patch in premenopausal women, with greater than or equal to 2.5% incidence over 6 to 13 menstrual cycles, include breast symptoms (including discomfort, engorgement, and/or pain; 22.4%), headaches (21.0%), application site reactions (17.1%), nausea (16.6%), abdominal pain (8.1%), dysmenorrhea (7.8%), vaginal bleeding and menstrual disorders (6.4%), mood, affect, and anxiety disorders (6.3%), vomiting (5.1%), diarrhea (4.2%), vaginal yeast infections (3.9%), dizziness (3.3%), acne (2.9%), migraine (2.7%), weight gain (2.7%), fatigue (2.6%), and pruritus (2.5%).[4] WP

Pharmacology

Pharmacodynamics

Norelgestromin is a progestogen. It is one of the active metabolites of norgestimate. Unlike many related progestins, norelgestromin reportedly has negligible androgenic activity. However, it produces levonorgestrel as an active metabolite to some extent, which does have some androgenic activity. Nonetheless, transdermally-administered norelgestromin does not counteract the increase in sex hormone-binding globulin levels produced by ethinyl estradiol.[4][5][6][12] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Pharmacokinetics

Upon application of a transdermal patch containing norelgestromin and ethinyl estradiol, plateau levels of both are reached by approximately 48 hours, and steady-state levels are reached within 2 weeks of application. Absorption following application to the buttock, upper outer arm, abdomen, and upper torso was assessed and, while absorption from the abdomen was slightly lower, it was considered to be therapeutically equivalent for the various areas. Mean levels of norelgestromin at steady-state ranged from 0.305 ng/mL to 1.53 ng/mL, with an average of about 0.725 ng/mL. The plasma protein binding of norelgestromin is 99%, and it is bound to albumin but not to sex hormone-binding globulin.[4][12][13][14] WP

The metabolism of norelgestromin takes place in the liver and is via transformation into levonorgestrel (conversion of the C3 oxime into a ketone) as well as hydroxylation and conjugation. However, because norelgestromin is used parenterally, first-pass metabolism in the liver and gastrointestinal tract that normally occurs with oral administration are avoided. The biological half-life of norelgestromin is 17 to 37 hours. The metabolites of norelgestromin, along with those of ethinyl estradiol, are eliminated in the urine and feces.[4][12][13] WP

Research

Research

A transdermal gel formulation of norgelstromin and ethinyl estradiol was under development by Antares Pharma for use as a method of birth control with the code name AP-1081 but development was discontinued.[15] WP

History

History

Norelgestromin was introduced for medical use in 2002.[7] WP

Legal status

Generic names

Norelgestromin is the generic name of the drug and its INN (International Nonproprietary Name), USAN (United States Adopted Name), and BAN (British Approved Name). The combined ethinyl estradiol and norelgestromin contraceptive patch is also known by its developmental code name RWJ-10553.[1][16] WP

Brand names

Norelgestromin is marketed under the brand names Evra, Ortho Evra, Xulane, and others, all in combination with ethinylestradiol.[1][10] WP

Availability

Norelgestromin is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Latin America, Asia, and elsewhere in the world. It is not listed as being marketed in Australia, New Zealand, Japan, South Korea, China, India, or certain other countries.[1] WP

Chemistry

Formula

C21H29NO2 PC

CAS number

53016-31-2 PC

Molar mass (g/mol)

327.5 PC

IUPAC name (computed by PubChem)

(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol PC

SMILES

CC[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC(=NO)CC[C@H]34 PC

InChIKey

ISHXLNHNDMZNMC-XUDSTZEESA-N PC

PubChem CID

62930

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Norelgestromin - brand name list from
2. Other Norelgestromin/Ethinyl Estradiol Patch
3. Journal / agency Crosignani PG, Nappi C, Ronsini S, Bruni V, Marelli S, Sonnino D. Satisfaction and compliance in hormonal contraception: the result of a multicentre clinical study on women's experience with the ethinylestradiol/norelgestromin contraceptive patch in Italy. BMC Women's Health. June 2009. doi:10.1186/1472-6874-9-18 · PMID 19566925 · PMC2714834
4. Journal / agency ORTHO EVRA (norelgestromin / ethinyl estradiol TRANSDERMAL SYSTEM). August 2012
5. Other Doherty AM. Annual Reports in Medicinal Chemistry. 2003
6. Other Offermanns S, Rosenthal W. Encyclopedia of Molecular Pharmacology. 14 August 2008
7. Other Macor JE. Annual Reports in Medicinal Chemistry. 2012
8. Other Borgelt LM. Women's Health Across the Lifespan: A Pharmacotherapeutic Approach. 2010
9. Other Vaamonde D, du Plessis SS, Agarwal A. Exercise and Human Reproduction: Induced Fertility Disorders and Possible Therapies. 7 March 2016
10. Other First Generic Ortho Evra Patch Launched. 17 April 2014
11. Journal / agency Galzote RM, Rafie S, Teal R, Mody SK. Transdermal delivery of combined hormonal contraception: a review of the current literature. International Journal of Women's Health. 2017. doi:10.2147/IJWH.S102306 · PMID 28553144 · PMC5440026
12. Journal / agency Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. August 2005. doi:10.1080/13697130500148875 · PMID 16112947
13. Journal / agency PREFEST (estradiol/norgestimate) tablets. November 2017
14. Journal / agency ORTHO-CYCLEN and ORTHO TRI-CYCLEN (norgestimate/ethinyl estradiol) tablets, for oral use. August 2017
15. Journal / agency Ethinylestradiol/Norelgestromin
16. Journal / agency Ethinylestradiol/Norelgestromin transdermal - Johnson & Johnson

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.