Norelgestromin

Source: Wikipedia, the free encyclopedia.
Norelgestromin
Clinical data
Trade namesEvra, Ortho Evra, Xulane, others
Other namesNorelgestromine; NGMN; RWJ-10553; Levonorgestrel 3-oxime; 17β-Deacetylnorgestimate; 17α-Ethynyl-18-methyl-19-nortestosterone 3-oxime; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime
AHFS/Drugs.comInternational Drug Names
MedlinePlusa602006
License data
Progestin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
conjugation)[4]
Metabolites• Levonorgestrel[4]
Elimination half-life17–37 hours[1][3]
ExcretionUrine and feces[4]
Identifiers
  • (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
JSmol)
  • ON=C4\C=C3/[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)CC)CC4
  • InChI=1S/C21H29NO2/c1-3-20-11-9-17-16-8-6-15(22-24)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23-24H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1 checkY
  • Key:ISHXLNHNDMZNMC-XUDSTZEESA-N checkY
  (verify)

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.[5][6][7] The medication is available in combination with an estrogen and is not available alone.[5] It is used as a patch that is applied to the skin.[6][7]

hormonal activity.[8][9]

Norelgestromin was introduced for medical use in 2002.[10] It is sometimes referred to as a "third-generation" progestin.[11][12] Norelgestromin is marketed widely throughout the world.[5] It is available as a generic medication.[13]

Medical uses

Norelgestromin is used in combination with

cervical mucus and endometrium that diminish the likelihood of pregnancy.[4]

Available forms

Norelgestromin is available only as a transdermal contraceptive patch in combination with ethinyl estradiol.[6] 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.[4][14]

Contraindications

See also:
Progestin § Contraindications

Side effects

See also:
Progestin § Side effects

Norelgestromin has mostly been studied in combination with an estrogen, so the

pruritus (2.5%).[4]

Overdose

See also:
Progestin § Overdose

Interactions

See also:
Progestin § Interactions

Pharmacology

Pharmacodynamics

Norelgestromin is a progestogen.[3][4] It is one of the active metabolites of norgestimate.[8][9] Unlike many related progestins, norelgestromin reportedly has negligible androgenic activity.[9] However, it produces levonorgestrel as an active metabolite to some extent, which does have some androgenic activity.[4][3] Nonetheless, transdermally-administered norelgestromin does not counteract the increase in sex hormone-binding globulin levels produced by ethinyl estradiol.[4]

Relative affinities (%) of norelgestromin and metabolites
Compound PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin
CBG
Tooltip Corticosteroid binding globulin
Norelgestromin 10 0 ? ? ? 0 ?
Levonorgestrel (3-keto-NGMN) 150–162 45 0 1–8 17–75 50 0
Notes: Values are percentages (%). Reference
CBGTooltip Corticosteroid-binding globulin. Sources: [15][3][16]

Pharmacokinetics

Upon application of a transdermal patch containing norelgestromin and ethinyl estradiol,

steady-state levels are reached within 2 weeks of application.[4] 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.[4] 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.[4] The plasma protein binding of norelgestromin is 99%, and it is bound to albumin but not to sex hormone-binding globulin.[1][2][3]

The

first-pass metabolism in the liver and gastrointestinal tract that normally occurs with oral administration are avoided.[4] The biological half-life of norelgestromin is 17 to 37 hours.[1][3] The metabolites of norelgestromin, along with those of ethinyl estradiol, are eliminated in the urine and feces.[4]

Chemistry

See also: List of progestogens

Norelgestromin, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime, is a

deacetyl derivative of norgestimate and is also known as levonorgestrel 3-oxime and as 17β-deacetylnorgestimate.[20] A related progestin is norethisterone acetate oxime (17α-ethynyl-19-nortestosterone 3-oxime 17β-acetate).[21]

History

Norelgestromin was introduced for medical use in 2002.[10]

Society and culture

Generic names

Norelgestromin is the

INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name.[5] The combined ethinyl estradiol and norelgestromin contraceptive patch is also known by its developmental code name RWJ-10553.[22]

Brand names

Norelgestromin is marketed under the brand names Evra, Ortho Evra, Xulane, and others, all in combination with ethinylestradiol.[5][13]

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.[5] It is not listed as being marketed in Australia, New Zealand, Japan, South Korea, China, India, or certain other countries.[5]

Research

A

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.[23]

See also

  • Ethinylestradiol/norelgestromin

References

  1. ^ a b c d "PREFEST (estradiol/norgestimate) tablets" (PDF). Teva Pharmaceuticals. U.S. Food and Drug Administration. November 2017.
  2. ^ a b "ORTHO-CYCLEN and ORTHO TRI-CYCLEN (norgestimate/ethinyl estradiol) tablets, for oral use" (PDF). Janssen Pharmaceuticals, Inc. U.S. Food and Drug Administration. August 2017.
  3. ^
    S2CID 24616324
    .
  4. ^ a b c d e f g h i j k l m n o p q r "ORTHO EVRA (norelgestromin / ethinyl estradiol TRANSDERMAL SYSTEM)" (PDF). Janssen Pharmaceuticals, Inc. U.S. Food and Drug Administration. August 2012.
  5. ^ a b c d e f g h "Norelgestromin - brand name list from". Drugs.com. Retrieved 2022-09-17.
  6. ^ a b c d "Norelgestromin/Ethinyl Estradiol Patch". Drugs.com.
  7. ^
    PMID 19566925
    .
  8. ^
    ISBN 978-0-12-040538-1
    .
  9. ^
    ISBN 978-3-540-38916-3
    .
  10. ^
    ISBN 978-0-12-396492-2
    .
  11. ISBN 978-1-58528-194-7
    .
  12. ISBN 978-1-4939-3402-7
    .
  13. ^ a b "First Generic Ortho Evra Patch Launched". Medical Professionals Reference (MPR). Haymarket Media, Inc. 17 April 2014.
  14. PMID 28553144
    .
  15. PMID 2170822
    .
  16. PMID 10599548
    .
  17. ^ US 7345183, Tombari DG, Vecchioli A, "Process for obtaining norelgestromin in different relations of isomers E and Z", issued 18 March 2008, assigned to Gador SA. 
  18. ISBN 978-1-284-05748-5
    .
  19. ISBN 978-1-59745-150-5
    .
  20. ISBN 978-92-832-1291-1
    .
  21. ISBN 978-1-4757-2085-3
    .
  22. ^ "Ethinylestradiol/Norelgestromin transdermal - Johnson & Johnson". AdisInsight. Springer Nature Switzerland AG.
  23. ^ "Ethinylestradiol/Norelgestromin". AdisInsight. Springer Nature Switzerland AG.

Further reading