Clinical data | |
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Trade names | Evra, Ortho Evra, Xulane, others |
Other names | Norelgestromine; 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.com | International Drug Names |
MedlinePlus | a602006 |
License data | |
Routes of administration | Transdermal patch |
Drug class | Progestogen; Progestin |
ATC code | |
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Pharmacokinetic data | |
Protein binding | 99% (to albumin but not to SHBG ) [1] [2] [3] |
Metabolism | Liver (oxime to ketone reaction, hydroxylation, conjugation) [4] |
Metabolites | • Levonorgestrel [4] |
Elimination half-life | 17–37 hours [1] [3] |
Excretion | Urine and feces [4] |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.170.714 |
Chemical and physical data | |
Formula | C21H29NO2 |
Molar mass | 327.468 g·mol−1 |
3D model (JSmol) | |
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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]
Side effects of the combination of an estrogen and norelgestromin include menstrual irregularities, headaches, nausea, abdominal pain, breast tenderness, mood changes, and others. [4] Norelgestromin is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. [8] [9] It has very weak androgenic activity and no other important 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]
Norelgestromin is used in combination with ethinyl estradiol in contraceptive patches. [6] [4] [7] 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. [4]
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]
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. [4] 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]
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]
Compound | PR | AR | ER | GR | MR | SHBG | CBG | |
---|---|---|---|---|---|---|---|---|
Norelgestromin | 10 | 0 | ? | ? | ? | 0 | ? | |
Levonorgestrel (3-keto-NGMN) | 150–162 | 45 | 0 | 1–8 | 17–75 | 50 | 0 | |
Notes: Values are percentages (%). Reference ligands (100%) were prome- gestone for the PR , metribolone for the AR , E2 for the ER , DEXA for the GR , aldosterone for the MR , DHT for SHBG , and cortisol for CBG . Sources: [15] [3] [16] |
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. [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 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. [4] However, because norelgestromin is used parenterally, 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]
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 synthetic estrane steroid and a derivative of testosterone. [5] It is a racemic mixture of E and Z isomers, which have approximately the same activity. [17] Norelgestromin is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins. [18] [19] It is the C3 oxime derivative of levonorgestrel and the C17β 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]
Norelgestromin was introduced for medical use in 2002. [10]
Norelgestromin is the generic name of the drug and its INN , USAN , and BAN . [5] The combined ethinyl estradiol and norelgestromin contraceptive patch is also known by its developmental code name RWJ-10553. [22]
Norelgestromin is marketed under the brand names Evra, Ortho Evra, Xulane, and others, all in combination with ethinylestradiol. [5] [13]
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]
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. [23]
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.
Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand names Plan B One-Step and Julie, among others, it is useful within 72 hours of unprotected sex. The more time that has passed since sex, the less effective the medication becomes, and it does not work after pregnancy (implantation) has occurred. Levonorgestrel works by preventing ovulation or fertilization from occurring. It decreases the chances of pregnancy by 57–93%. In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy. A levonorgestrel-releasing implant is also available in some countries.
A contraceptive patch, also known as "the patch", is a transdermal patch applied to the skin that releases synthetic oestrogen and progestogen hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.
Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.
Desogestrel is a progestin medication which is used in birth control pills. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.
Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.
Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.
Norgestimate, sold under the brand names Ortho Tri-Cyclen and Previfem among others, is a progestin medication which is used in birth control pills for women and in menopausal hormone therapy. The medication is available in combination with an estrogen and is not available alone. It is taken by mouth.
Norgestrel is a progestin which is used in birth control pills sold under the brand name Ovral in combination with the estrogen ethinylestradiol and Opill by itself. It is also used in menopausal hormone therapy. It is taken by mouth.
An estrogen patch, or oestrogen patch, is a transdermal delivery system for estrogens such as estradiol and ethinylestradiol which can be used in menopausal hormone therapy, feminizing hormone therapy for transgender women, hormonal birth control, and other uses. Transdermal preparations of estrogen are metabolized differently than oral preparations. Transdermal estrogens avoid the first pass through the liver and thus potentially reduce the risk of blood clotting and stroke.
Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a progestin medication which is used in birth control pills. The medication is available only in combination with an estrogen. It is taken by mouth.
Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.
Gestodene, sold under the brand names Femodene and Minulet among others, is a progestin medication which is used in birth control pills for women. It is also used in menopausal hormone therapy. The medication is available almost exclusively in combination with an estrogen. It is taken by mouth.
Dienogest, sold under the brand name Visanne among others, is a progestin medication which is used in birth control pills and in the treatment of endometriosis. It is also used in menopausal hormone therapy and to treat heavy periods. Dienogest is available both alone and in combination with estrogens. It is taken by mouth.
Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of hormonal birth control which is used to prevent pregnancy in women. It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women. Each dose of this form lasts two months with only up to two doses typically recommended.
Segesterone acetate (SGA), sold under the brand names Nestorone, Elcometrine, and Annovera, is a progestin medication which is used in birth control and in the treatment of endometriosis in the United States, Brazil, and other South American countries. It is available both alone and in combination with an estrogen. It is not effective by mouth and must be given by other routes, most typically as a vaginal ring or implant that is placed into fat.
Norelgestromin/ethinylestradiol, sold under the brand name Ortho Evra among others, is a contraceptive patch containing the progestin norelgestromin and the estrogen ethinylestradiol.
Levonorgestrel acetate (LNG-A), or levonorgestrel 17β-acetate, also known as 3-ketonorgestimate, is a progestin which was never marketed. It is a progestogen ester and is the C17β acetate ester and a prodrug of levonorgestrel. Norgestimate is the C3 oxime of LNG-A. The drug is a minor active metabolite of norgestimate, which is a prodrug of norelgestromin and to a lesser extent of levonorgestrel and LNG-A. LNG-A has high affinity for the progesterone receptor, about 135% of that of promegestone. Along with levonorgestrel butanoate, LNG-A was investigated as a hormonal contraceptive by the Population Council.
Combined hormonal contraception (CHC), or combined birth control, is a form of hormonal contraception which combines both an estrogen and a progestogen in varying formulations.