Norethisterone


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Menorrhagia 5 mg bid-tid from the 19th -26th day of cycle (count the 1st day of menstruation as day 1). Endometriosis 10-20 mg daily starting between 1st and 5th day of the cycle, continuously for 4-6 months. As norethisterone acetate: 5-15 mg daily, start at 5 mg daily and increase by 2.5 mg at 14-day intervals; take continuously for 6-9 months. Contraception 0.35 mg daily. Premenstrual syndrome 5 mg tid on days 19-26 of the cycle. Dysfunctional uterine bleeding 5 mg tid for 10 days; 5 mg bid from the 19th-26th day of the 2 subsequent cycles to prevent recurrence of the condition. As norethisterone acetate: 2.5-10 mg daily for 5-10 days. Postponement of menstruation 5 mg tid for up to 14 days starting 3 days before expected onset of menstruation. Dysmenorrhoea 5 mg tid for 20 days, starting on the 5th day of the cycle (count the 1st day of menstruation as day 1). IM Contraception As norethisterone enantate: 200 mg given within first 5 days of menstrual cycle every 8 weeks.
Dosage Details
Intramuscular
Contraception
Adult: As norethisterone enantate: 200 mg given within the first 5 days of menstrual cycle (counting the 1st day as day 1) or immediately after giving birth, may repeat dose every 8 weeks.

Oral
Postponement of menstruation
Adult: 5 mg tid for up to 14 days, starting 3 days before expected onset of menstruation.

Oral
Dysfunctional uterine bleeding
Adult: 5 mg tid for 10 days. For prevention of recurrence: 5 mg bid from the 19th-26th day of the 2 subsequent cycles. As norethisterone acetate: 2.5-10 mg daily for 5-10 days.

Oral
Menorrhagia
Adult: 5 mg bid-tid from the 19th-26th day of cycle (count the 1st day of menstruation as day 1).

Oral
Endometriosis
Adult: 10-20 mg daily starting between 1st and 5th day of the cycle, continuously for 4-6 months or longer. As norethisterone acetate: 5-15 mg daily; start at 5 mg daily and increase by 2.5 mg at 14-day intervals; take continuously for 6-9 months.

Oral
Premenstrual syndrome
Adult: 5 mg bid-tid on days 19th-26th day of the cycle. May repeat treatment for several cycles.

Oral
Contraception
Adult: 0.35 mg daily, starting on the 1st day of menstruation, or on the day after abortion or miscarriage, or on the 21st day after childbirth. Take continuously as long as contraception is desired.

Oral
Dysmenorrhoea
Adult: 5 mg tid for 20 days, starting on the 5th day of the cycle (count the 1st day of menstruation as day 1). Maintain treatment for 3-4 cycles followed by treatment-free cycles.
Administration
May be taken with or without food.
Contraindications
Known, suspected, or history of breast cancer or endometrial cancer, active or recent arterial thromboembolic disease (e.g. stroke, MI), current or history of venous thromboembolism (e.g. DVT, pulmonary embolism), angina pectoris, undiagnosed vaginal bleeding, porphyria, benign or malignant hepatic tumour; severe diabetes with vascular changes, pathologically increased blood pressure (as norethisterone enantate). Hepatic impairment or disease (e.g. Dubin-Johnson syndrome, Rotor syndrome). Pregnancy.
Special Precautions
Patient with risk factors for cardiovascular disease (e.g. hypercholesterolaemia, hypertension, obesity), and/or venous thromboembolism (e.g. personal or family history of venous thromboembolism, SLE, prolonged immobilisation); depression, diabetes mellitus, conditions that may be aggravated by fluid retention (e.g. asthma, migraine, epilepsy, cardiac dysfunction). Smokers. Renal impairment. Lactation.
Adverse Reactions
Significant: Irregular menstrual bleeding, breast cancer, visual abnormalities (e.g. partial or complete loss of vision, proptosis, diplopia), migraine, depression, decreased glucose tolerance, venous thromboembolism (e.g. deep vein thrombosis). Rarely, benign or malignant liver tumour.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain.
General disorders and administration site conditions: Fatigue.
Hepatobiliary disorders: Cholestatic jaundice.
Immune system disorders: Hypersensitivity.
Investigations: Weight gain, abnormal LFT.
Metabolism and nutrition disorders: Oedema.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Insomnia.
Reproductive system and breast disorders: Breast tenderness, amenorrhoea, spotting, decreased libido, change in cervical secretions, cervical erosion, breast hypertrophy.
Skin and subcutaneous tissue disorders: Acne, chloasma, pruritus, urticaria.
MonitoringParameters
Assess pregnancy status prior to therapy, diagnostic measures (e.g. endometrial sampling). Monitor weight, vision changes (e.g. loss of vision, diplopia), signs or symptoms of depression, glycaemic control (in diabetic patients), lipid profile (patients treated for hyperlipidaemia). Perform breast and pelvic examination (e.g. Papanicolaou smear), as necessary.
Overdosage
Symptoms: Nausea, vomiting, breast enlargement, vaginal bleeding. Management: Symptomatic treatment. May employ gastric lavage within 4 hours of ingestion in case of large overdose.
Drug Interactions
Decreased therapeutic effect with barbiturates, phenytoin, carbamazepine, griseofulvin, felbamate. Increased plasma concentrations with CYP3A4 inhibitors (e.g. ketoconazole, erythromycin, verapamil, diltiazem). May reduce the therapeutic effect of ulipristal.
Food Interaction
Diminished therapeutic effect with St. John’s wort.
Lab Interference
May interfere with tests for binding proteins (e.g. thyroid-binding globulin), glucose metabolism, coagulation, and LFT. May reduce the response to metyrapone test.
Action
Description: Norethisterone has typical effects of a progestogen and converts the endometrium from the proliferative to the secretory phase. It inhibits the secretion of the pituitary gonadotropins thus preventing follicular maturation and ovulation. In addition, it increases the cervical mucous viscosity and alters the endometrium resulting to impaired implantation and blocked sperm penetration, respectively.
Synonym: Norethindrone.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 64%. Time to peak plasma concentration: Approx 1-2 hours.
Distribution: Enters breastmilk. Volume of distribution: 4 L/kg. Plasma protein binding: Approx 60% to albumin; 35% to sex hormone binding globulin.
Metabolism: Undergoes extensive hepatic first-pass effect Norethisterone acetate is deacetylated to norethisterone which further undergoes hepatic reduction and conjugation. Norethisterone is also metabolised to ethinylestradiol.
Excretion: Via urine (>50%, as metabolites); faeces (20-40%, as metabolites). Elimination half-life: Approx 8-9 hours.
Chemical Structure

Chemical Structure Image
Norethisterone

Source: National Center for Biotechnology Information. PubChem Database. Norethindrone, CID=6230, https://pubchem.ncbi.nlm.nih.gov/compound/Norethindrone (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C. Protect from light.
ATC Classification
G03DC02 - norethisterone ; Belongs to the class of estren derivative progestogens used in progestogenic hormone preparations.
G03AC01 - norethisterone ; Belongs to the class of progestogens. Used as systemic contraceptives.
References
Anon. Norethindrone Acetate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/12/2019.

Anon. Norethindrone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/12/2019.

Buckingham R (ed). Norethisterone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/12/2019.

Joint Formulary Committee. Norethisterone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/12/2019.

Norethindrone 0.35 mg Tablet (Lupin Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 29/01/2020.

Norethindrone Acetate Tablet (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/12/2019.

Norethindrone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com/. Accessed 09/12/2019.

Disclaimer: This information is independently developed by MIMS based on Norethisterone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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