Drug Nomenclature
Synonyms: Ethinylnortestosterone; NSC-9564; Norethindrone; Norethisteron; Norethisteronum; Noretisteron; Noretisterona; Noretisteronas; Noretisterone; Noretisteroni; Noretiszteron; NorpregneninolonePharmacopoeias. In China, Europe, International, Japan, and US.
European Pharmacopoeia, 6th ed. (Norethisterone). A white or yellowish-white crystalline powder. Practically insoluble in water sparingly soluble in dehydrated alcohol and in acetone soluble in dichlorometh-ane.
The United States Pharmacopeia 31, 2008 (Norethindrone). A white to creamy-white odourless crystalline powder. Practically insoluble in water sparingly soluble in alcohol soluble in chloroform and in dioxan slightly soluble in ether.
Norethisterone Acetate
Drug Nomenclature
Pharmacopoeias. In Europe, International, and US.
European Pharmacopoeia, 6th ed. (Norethisterone Acetate). A white or yellowish-white crystalline powder. It exhibits polymorphism. Practically insoluble in water soluble in alcohol freely soluble in dichloromethane. Protect from light.
The United States Pharmacopeia 31, 2008 (Noneth in drone Acetate). A white to creamy-white odourless crystalline powder. Practically insoluble in water soluble 1 in 10 of alcohol, 1 in less than 1 of chloroform, 1 in 2 of dioxan, and 1 in 18 of ether.
Norethisterone Enantate
Drug Nomenclature
Pharmacopoeias. In International
Adverse Effects and Precautions
As for progestogens in general (see Progesterone). See also under Hormonal Contraceptives.
Effects on the liver
There were 6 cases of jaundice among 107 patients with breast cancer treated with high-dose norethisterone acetate the jaundice was reversible and of an obstructive type. A retrospective analysis found that the use of norethisterone to prevent menstrual haemorrhage during the thrombocytopenic phase of allogeneic bone marrow transplantation was a significant risk factor for hepatic veno-occlusive disease.
Porphyria
Norethisterone has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
Pregnancy
Abnormalities seen in the offspring of women given norethisterone during pregnancy (either alone or with ethinylestradiol) included: hypospadias, masculinisation of female infants, meningomyelocele or hydrocephalus, and neonatal choreoathetosis associated with oral contraceptive use. For reference to the fact that oral contraceptives have not generally been associated with teratogenicity, even when used inadvertently in pregnancy.
Venous thromboembolism
For mention that combined oral contraceptives containing older progestogens such as norethisterone appear to be associated with a lower incidence of venous thromboembolism than desogestrel- or gestodene-containing preparations.
Interactions
As for progestogens in general (see Progesterone). See also under Hormonal Contraceptives.
Pharmacokinetics
Norethisterone is absorbed from the gastrointestinal tract, undergoing first-pass hepatic metabolism, with peak plasma concentrations occurring 1 to 2 hours after an oral dose. It exhibits biphasic pharmacokinetics an initial distribution phase is followed by a prolonged elimination phase with a half-life of about 8 hours or more. Norethisterone is highly protein bound about 60% to albumin and 35% to sex hormone binding globulin. Use with an oestrogen increases the proportion bound to sex hormone binding globulin. It is metabolised in the liver with 50 to 80% of a dose being excreted in the urine and up to 40% appearing in the faeces.
Norethisterone acetate is rapidly hydrolysed to norethisterone, principally by intestinal tissue. After intramuscular injection of norethisterone enantate peak concentrations of norethisterone in plasma are not attained for several days.
Uses and Administration
Norethisterone and its acetate and enantate esters are progestogens (see Progesterone) derived from nortestosterone that have weak oestrogenic and andro-genic properties. They are commonly used as hormonal contraceptives. Norethisterone and norethisterone acetate are both given orally. Typical daily doses are 350 micrograms for norethisterone and 600 micrograms for norethisterone acetate when used alone, or 0.5 to 1 mg for norethisterone and 1 to 1.5 mg for norethisterone acetate when used with an oestrogen. Norethisterone enantate is given by intramuscular injection a dose of 200 mg provides contraception for 8 weeks. An intramuscular injection containing norethisterone enantate 50 mg with estradiol valerate 5 mg is given once each month.
Norethisterone and norethisterone acetate are used as the progestogen component of menopauasl HRT. Typical regimens have included either continuous daily doses of norethisterone 700 micrograms or norethisterone acetate 0.5 to 1 mg, or cyclical regimens of norethisterone or norethisterone acetate 1 mg daily for 10 to 12 days of a 28-day cycle. Norethisterone acetate is also available as transdermal patches supplying 140, 170, or 250 micrograms in 24 hours, that are applied twice weekly for 2 weeks of a 4-week cycle the lower strengths may also be applied twice weekly on a continuous basis.
Norethisterone and norethisterone acetate may be given orally, usually in divided doses, for the treatment of conditions such as menorrhagia (below) and endometriosis. In menorrhagia (dysfunctional uterine bleeding), norethisterone is given in usual doses of 10 to 15 mg daily and norethisterone acetate in doses of 2.5 to 10 mg daily, in a cyclical regimen. In endometriosis the dosage of norethisterone is 10 to 25 mg daily and of norethisterone acetate 5 to 15 mg daily. Treatment of endometriosis is usually continuous for 4 to 9 months.
Norethisterone has been used in daily doses of up to 15 mg orally in a cyclical regimen in the treatment of premenstrual syndrome. In breast cancer oral doses of up to 60 mg daily of norethisterone have been used.
Administration in children
Although unlicensed in the UK for use in children, the BNFC does include norethisterone for the management of delayed puberty in girls. It is added after 12 to 24 months of oestrogen therapy to establish a menstrual cycle and maintain sexual maturation, in an oral dose of 5 mg once daily for the last 7 days of a 28-day cycle.
Menorrhagia
Although cyclical norethisterone has been widely used for menorrhagia, it is of limited efficacy during ovulatory cycles being most effective for anovulatory bleeding, which occurs in a minority of women with menorrhagia.
Preparations
British Pharmacopoeia 2008: Estradiol and Norethisterone Acetate Tablets; Estradiol and Norethisterone Tablets; Norethisterone Tablets
The United States Pharmacopeia 31, 2008: Estradiol and Norethindrone Acetate Tablets; Norethindrone Acetate and Ethinyl Estradiol Tablets; Norethindrone Acetate Tablets; Norethindrone and Ethinyl Estradiol Tablets; Norethindrone and Nestranol Tablets; Norethindrone Tablets.
Proprietary Preparations
Argentina: Ginediol Primolut-Nor Selectan
Australia: Locilan Nicronor Noriday Primolut N
Austria: Duokliman Nicronovum Primolut-Nor
Belgium: Primolut-Nor
Brazil: Nicronor Norestin Primolut-Nor
Canada: Nicronor Norlutate
Chile: Primolut-Nor
Czech Republic: Primolut-Nor
Denmark: Mini-Pe
Finland: Mini-Pill Primolut N Primolut-Nor
France: Milligynon Primolut-Nor
Germany: Gestakadin Noristerat Primolut-Nor Sovel
Greece: Fortilut Primolut-Nor
Hong Kong: Norcolut Primolut N
Hungary: Norcolut
India: Cycloreg Noristerat Norlut Primolut N Styptin
Indonesia: Anore Norelut Primolut N Regumen
Ireland: Noriday Primolut N
Israel: Primolut-Nor
Italy: Primolut-Nor
Malaysia: Depocon Norcolut Noriday Noristerat Primolut N Sunolut Trisequens
Mexico: Noristerat Primolut-Nor
The Netherlands: Primolut N
Norway: Conluclag Primolut N
New Zealand: Noriday Primolut N
Philippines: Noristerat Primolut N
Poland: Primolut-Nor
Portugal: Primolut-Nor
Russia: Primolut-Nor
South Africa: Nicronovum Nur-Isterate Primolut N
Singapore: Norcolut Noristerat Primolut N
Spain: Primolut-Nor
Sweden: Nini-Pe Primolut-Nor
Switzerland: Nicronovum Primolut N
Thailand: Noristerat Primolut N Steron
Turkey: Primolut N
UK: Nicronor Nicronor HPT Noriday Noristerat Primolut N Utovlan
USA: Aygestin Jolivette Nor-QD Ortho Nicronor
Multi-ingredient
Argentina: Activelle Estalis Estalis Sequi Estracomb Estragest Evorel Conti Evorel Sequi Kliogest Nesigyna Trial Combi Trial Gest Trial Pack Trisequens
Australia: Brevinor Estalis Continuous Estalis Sequi Estracombi Improvil Kliogest Kliovance Norimin Norinyl-1 Synphasic Trisequens
Austria: Activelle Estalis Estalis Sequens Estracomb Fem-HRT Kliogest Nericomb Nerigest Novofem Ovysmen Perikliman Primosiston Trinovum Trisequens
Belgium: Activelle Estalis Estracombi Kliogest Minestril Novofem Ovysmen Trinovum Trisequens
Brazil: Activelle Biofim Ciclovulon Cliane Estalis Estalis SQ Estracomb Estragest Gineane Ginedisc 50 Plusf Kliogest Negestran Nericomb Nerigest Nesigyna Natifa Pro Noregyna Primosiston Suprema Systen Conti Systen Sequi Trinovum Trisequens
Canada: Brevicon Estalis Estalis Sequi Estracomb FemHRT Loestrin 1.5/30 Ninestrin Ortho 0.5/35 Ortho 1/35 Ortho 7/7/7 Ortho-Novum 1/50 Select 1/35 Synphasic
Chile: Activelle Cliane Enadiol Neta Estracomb Estragest Ginefolin Kliogest Nesigyna Primosiston Trisequens
Czech Republic: Activelle Estalis Estalis Sequi Estrace Plus Estrace-C Estracomb Estragest Kliane Kliogest Nenophase Non-Ovlon Novofem Pausogest Sequidot Systen Conti Systen Sequi Triaklim Trinovum Trisequens
Denmark: Activelle Econ Estracomb Evo-Conti Evo-Sequi Femanor Femasekvens Kliogest Novofem Ostranorm Trinorm Trinovum Trisekvens
Finland: Activelle Estalis Estalis Sekvens Estracomb Evorel Conti Evorel Sequi Kliogest Nericomb Nerigest Novofem Trisekvens
France: Activelle Kliogest Niniphase Novofemme Ortho-Novum 1/35 Triella Trisequens
Germany: Activelle Clionara Conceplan N Estalis Sequi Estracomb Estragest Eve Gynamon Kliogest N Nericomb Nerigest Non-Ovlon Nora-ratiopharm Novofem Ostro-Primolut Ovysmen Primosiston Prosiston Sequostat Sinovula Synphasec Trinovum Trisequens
Greece: Activelle Estalis Estracomb TTS Kliogest Systen Conti Systen Sequi Trisequens
Hong Kong: Activelle Brevinor Estracomb Kliogest Norimin Norinyl-1 Novofem Synphase Trinovum Trisequens
Hungary: Activelle Estracomb Estragest Kliogest Pausogest Triaklim Trisequens Tulita
Ireland: Activelle Brevinor Estalis Estalis Sequi Estracombi Estrapak Evorel Conti Kliogest Novofem Trisequens
Israel: Activelle Evorel Conti Evorel Sequi Kliogest Neno-Net Novofem Trisequens
Italy: Activelle Estalis Sequi Estracomb Kliogest Trisequens
Japan: Ortho 777
Malaysia: Activelle Kliogest
Mexico: Cliane Estalis Estracomb Evorel Conti Nesigyna Norace Norinyl Nostidyn Ortho-Novum 1/35 Ortho-Novum
The Netherlands: Activelle Estalis Estalis Sequi Estracomb Kliogest Nodicon Neocon Novofem Trinovum Trisequens
Norway: Activelle Estalis Estalis Sekvens Kliogest Novofem Synfase Trisekvens
New Zealand: Brevinor Cliane Estrapak Kliogest Kliovance Norimin Norinyl-1 Synphasic Trisequens
Philippines: Kliogest Nicropil
Poland: Activelle Estalis Estalis Sequi Estracomb Kliogest Novofem Systen Conti Systen Sequi Trinovum Trisequens
Portugal: Activelle Estalis Estalis Sequi Estracomb Kliogest Novofem Trisequens
Russia: Non-Ovlon Pausogest Triaklim Trisequens
South Africa: Activelle Brevinor Estracombi Estro-Pause N Evorel Conti Evorel Sequi Kliogest Norinyl-1/28 Novofem Trinovum Trisequens
Singapore: Activelle Estracomb Kliogest Trisequens
Spain: Absorlent Plus Activelle Duofemme Endomina Plus Estalis Estalis Sequi Estracomb Nerigest Nerigest Sequi Trisequens
Sweden: Activelle Estalis Estalis Sekvens Estracomb Evorel Nicronor Femanor Femasekvens Kliogest Novofem Orthonett Novum Synfase Trinovum Trisekvens
Switzerland: Activelle Estalis Estalis Sequi Estracomb Estragest Kliogest N Nericomb Nerigest Novofem Ovysmen Primosiston Systen Conti Systen Sequi Trinovum Trisequens
Thailand: Activelle Anamai
Turkey: Activelle Estracombi Kliogest Nesigyna Trisequens
UK: Binovum Brevinor Climagest Climesse Clinorette Elleste Duet Conti Elleste-Duet Estracombi Estrapak Evorel Conti Evorel Pak Evorel Sequi FemTab Continuous Kliofem Kliovance Loestrin Norimin Norinyl-1 Novofem Nuvelle Continuous Ovysmen Synphase Trinovum Trisequens
USA: Activella Aranelle Balziva Brevicon CombiPatch Estrostep Fe Estrostep Femcon Fe FemHRT Junel Fe Leena Loestrin Loestrin Fe Nodicon Necon 1/50 Necon 10/1 I Necon 0.5/35, 1/35 NEE 1/35 Norinyl I + 35 Norinyl I + 50 Ortho-Novum 1/35 Ortho-Novum 1/50 Ortho-Novum 10/11 Ortho-Novum 7/7/7 Ovcon 35 Ovcon 50 Tilia Fe Tri-Legest Tri-Norinyl Zenchent
Venezuela: Cliane Estracomb Estragest Nesigyna Primosiston-F.
Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.