Nomegestrol, a related compound, was patented in 1975, and NOMAC was described in 1983.[15][16] NOMAC was first introduced for medical use, for the treatment of gynecological disorders and in menopausal hormone therapy, in
Europe in 1986.[1][17][18] It was subsequently approved in Europe in 2011 as a component of birth control pills.[1][17][18] NOMAC is available widely throughout the world.[8][19] It is not available in the
United States or
Canada.[8][1][17][18]
There have been no reports of serious
adverse effects due to
overdose of NOMAC.[7] NOMAC has been administered alone at a dosage of up to 40 times the recommended dosage, and the combination of NOMAC and estradiol has been administered in multiple doses of up to 5 times the recommended dosage to women in clinical trials, and no safety concerns or harmful effects were observed in either case.[28][7] Symptoms of NOMAC and estradiol overdose might include
nausea,
vomiting, and, in young girls, slight
vaginal bleeding.[7] There is no
antidote for NOMAC overdose and treatment of overdose should be based on
symptoms.[7]
Notes: Values are percentages (%). Reference
ligands (100%) were
promegestone for the
PRTooltip progesterone receptor,
metribolone for the
ARTooltip androgen receptor,
estradiol for the
ERTooltip estrogen receptor,
dexamethasone for the
GRTooltip glucocorticoid receptor,
aldosterone for the
MRTooltip mineralocorticoid receptor,
dihydrotestosterone for
SHBGTooltip sex hormone-binding globulin, and
cortisol for
CBGTooltip Corticosteroid-binding globulin. Sources:[3]
Like many other
progestogens,[34][35] NOMAC has been assessed and found in vitro to inhibit the conversion of
estrone sulfate to
estrone (via inhibition of
steroid sulfatase) and estrone to estradiol (via inhibition of
17β-HSDTooltip 17β-hydroxysteroid dehydrogenase) at high concentrations (0.5–50 μM) and to stimulate the conversion of estrone into estrone sulfate (via activation of
estrogen sulfotransferase activity) at low concentrations (0.05–0.5 μM), whilst not affecting
aromatase activity at any tested concentration (up to 10 μM).[1][5] These activities appear to be PR-dependent, as NOMAC is more potent in producing them in PR-rich cell lines (e.g.,
T47-D vs.
MCF-7) and they can be blocked by the PR antagonist
mifepristone (RU-486).[5] Although the clinical implications of these actions are unclear and they have yet to be confirmed in vivo or assessed in
clinical studies, it has been suggested that NOMAC and certain other progestins may be useful in the treatment of
ERTooltip estrogen receptor-positive
breast cancer by decreasing levels of
estrogens in breast tissue.[34][35] In accordance with this notion, in vitro, NOMAC does not have proliferative effects on breast tissue, does not stimulate breast cell proliferation via
PGRMC1Tooltip progesterone receptor membrane component 1 (similarly to progesterone), and reduces the breast proliferative effects of estradiol when added to it in medium.[36]
Antigonadotropic effects
The
ovulation-inhibiting dosage of NOMAC is 1.5 to 5 mg/day.[1][3][37] Due to its high antigonadotropic activity and its long elimination half-life, the contraceptive effectiveness of NOMAC is maintained even when a dose is missed; clinical studies found no increased incidence of
pregnancy with one missed pill of Zoely or even with two missed pills during days 8 to 17 of the
menstrual cycle.[2]
Nomegestrol was patented in 1975, and NOMAC, under the developmental code name TX-066, was first described in the literature in 1983.[15][16] It was developed by Theramex Laboratories, a
pharmaceutical company in
Monaco (a satellite country of
France).[1] The medication was first introduced in Europe alone or in combination with estradiol under the respective brand names Lutenyl and Naemis[5] for the treatment of gynecological disorders and menopausal symptoms in 1986, and was subsequently developed and approved in 2011 in Europe as a birth control pill in combination with estradiol under the brand name Zoely.[1][17][18] As Zoely, NOMAC has been studied in over 4,000 women as a method of birth control.[2]
Society and culture
Generic names
Nomegestrol acetate is the
generic name of the drug and its
INNTooltip International Nonproprietary Name,
USANTooltip United States Adopted Name, and
BANTooltip British Approved Name.[15][19][8] It is also known by its former developmental code name TX-066.[15][19][8]
Brand names
NOMAC is marketed in combination with estradiol as a birth control pill primarily under the brand name Zoely, in combination with estradiol for use in menopausal hormone therapy primarily under the brand name Naemis, and as a standalone medication for use in menopausal hormone therapy and the treatment of gynecological disorders primarily under the brand name Lutenyl.[8] NOMAC is also marketed alone or in combination with estradiol under a variety of other less common brand names throughout the world.[8]
Under the tentative brand name Uniplant, NOMAC was under development by Theramex as a 38 mg or 55 mg 4 cm
Silastic (
silicone-
plastic)
subcutaneousbirth control implant of one-year duration (75 ug/day or 100 μg/day release rate) in
Brazil from the 1990s and was extensively studied for this purpose in
clinical trials.[10][11][12][13] The clinical studies included 19,900 women-months of use and demonstrated a one-year failure rate of 0.94%. Uniplant was regarded as showing high effectiveness, and was well tolerated.[13] In spite of this however, "[f]urther plans to make it available have been deferred by decision of the company holding the progestin patent",[51] and, although it continued to be investigated as late as 2006,[52] the implant ultimately never became commercially available.[53][54]
Oral NOMAC was under development for the treatment of
breast cancer and for use as a
progestogen-only pill for birth control but did not complete development for these indications.[55] An estradiol and NOMAC
vaginal ring was under development for use in birth control and to treat
dysmenorrhea but did not complete development and was not marketed.[56] A continuous oral formulation of estradiol and NOMAC was under development for the treatment of menopausal symptoms and the treatment or prevention of
postmenopausal osteoporosis but did not complete development.[57]
^
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^Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, et al. (November 2012). "Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology". Annales d'Endocrinologie. 73 (5): 469–487.
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^Lyseng-Williamson KA, Yang LP, Plosker GL (2012). "Nomegestrol acetate/estradiol: a guide to its use in oral contraception". Drugs & Therapy Perspectives. 29 (1): 1–6.
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abPasqualini JR (December 2009). "Breast cancer and steroid metabolizing enzymes: the role of progestogens". Maturitas. 65 (Suppl 1): S17–S21.
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10.1016/j.maturitas.2009.11.006.
PMID19962254.
^Del Pup L, Berretta M, Di Francia R, Cavaliere C, Di Napoli M, Facchini G, et al. (August 2014). "Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk". Anti-Cancer Drugs. 25 (7): 745–750.
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^Wiegratz I, Kuhl H (September 2006). "Metabolic and clinical effects of progestogens". The European Journal of Contraception & Reproductive Health Care. 11 (3): 153–161.
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