Norethisterone enanthate

Pharmacodynamics

NETE is a prodrug of norethisterone in the body.^[13] Upon reaching circulation, it is rapidly converted into norethisterone by esterases. Hence, as a prodrug of norethisterone, NETE has essentially the same effects as norethisterone, acting as a potent progestogen with additional weak androgenic and estrogenic activity (the latter via its metabolite ethinylestradiol).^[14] NETA has some progestogenic activity of its own, but it is unclear if NETE does similarly.^[13]

NETE is of about 38% higher molecular weight than norethisterone due to the presence of its C17β enanthate ester.^[2]

A single intramuscular injection of estradiol valerate/norethisterone enanthate (5 mg/50 mg) (Mesigyna) has been found to strongly suppress testosterone levels in men.^[34] Levels of testosterone decreased from ~503 ng/dL at baseline to ~30 ng/dL at the lowest point (–94%).^[34]

Pharmacokinetics

A single intramuscular injection of 50 to 200 mg NETE in oil solution has been found to have a duration of action of 11 to 52 days in terms of clinical biological effect in the uterus and on body temperature in women.^[36]

Similarly to oral norethisterone and norethisterone acetate, intramuscular NETE has been found to form ethinylestradiol as an active metabolite.^[35] With a single intramuscular injection of 200 mg NETE in premenopausal women, the mean maximum concentration of ethinylestradiol was 32% of that of a combined oral contraceptive containing 30 μg ethinylestradiol, the maximum equivalent oral dose of ethinylestradiol observed in the first few days of exposure was 20.3 μg/day, and the mean equivalent oral dose of ethinylestradiol over 8 weeks was 4.41 μg/day.^[35] As such, the exposure to ethinylestradiol was described as markedly lower than that of an oral contraceptive containing 30 μg ethinylestradiol.^[35] The estimated conversion rate of NETE into ethinylestradiol was 0.1%, which was much lower than that observed for oral norethisterone and norethisterone enanthate (0.2–1.0%), likely due to the lack of the first pass through the liver with parenteral administration.^[35] In accordance with the low levels of ethinylestradiol produced, no increase rates of thromboembolism or hepatic adenoma have been observed in post-authorization data of intramuscular NETE, and the medication does not resemble combined oral contraceptives containing ethinylestradiol in its safety profile.^[35]

Generic names

Norethisterone enantate is the generic name of the drug and its INNMTooltip International Nonproprietary Name and BANMTooltip British Approved Name.^{[2][37][39][40][41]} It is also spelled as norethisterone enanthate and is also known as norethindrone enanthate (the USANTooltip United States Adopted Name of norethisterone being norethindrone).^{[2][37][39][40][41]} NETE is known by its former developmental code name SH-393 as well.^{[2][37][39][40][41]}

Brand names

NETE has been marketed alone as a progestogen-only injectable contraceptive under the brand names Depocon, Doryxas, NET-EN, Noristat, Noristerat, Norigest, and Nur-Isterate, and in combination with estradiol valerate as a combined injectable contraceptive under the brand names Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, and Solouna.^{[37][40][41][42]}

Availability

NETE has been approved for use alone as a progestogen-only injectable contraceptive in more than 60 countries throughout the world including in Europe, Latin America, Asia, and Africa.^[4][10][11] Specific countries in which NETE as a standalone medication is or has been available include Bangladesh, France, Germany, India, Italy, Malaysia, Mexico, the Philippines, Singapore, South Africa, Thailand, and the United Kingdom.^{[37][40][41][42]}

NETE has been approved for use in combination with estradiol valerate as a combined injectable contraceptive in at least 36 countries, mostly in Latin America but also in Africa.^[11][12] It is or has been available in combination with estradiol valerate in Argentina, the Bahamas, Barbados, Bolivia, Brazil, Chile, Colombia, Costa Rica, the Dominican Republic, Ecuador, Egypt, El Salvador, Ghana, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Kenya, Mexico, Nicaragua, Panama, Paraguay, Peru, St. Lucia, Turkey, Uruguay, Venezuela, and Zimbabwe.^{[40][41][42][14]}

NETE is not available in any form in the United States.^[10]