Adult: As norethisterone enantate: 200 mg as a single dose given within the 1st 5 days of menstrual cycle (counting the 1st day of menstruation as day 1) or immediately after delivery; dose may be repeated after 8 weeks. Doses are given via slow IM inj deep into the gluteal muscle.
Oral Endometriosis
Adult: As norethisterone base: 10-15 mg daily in 2-3 divided doses, starting between the 1st and 5th day of menstrual cycle; if spotting occurs, increase dose to 20-25 mg daily then reduce to the initial dose once bleeding has stopped. Continue treatment for 4-6 months or longer. As norethisterone acetate: Initially, 5 mg daily for 14 days, then increased by 2.5 mg daily every 2 weeks until 15 mg daily is achieved. Continue therapy for 6-9 months. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Contraception
Adult: As norethisterone base: 0.35 mg once daily, exactly as directed on the blister pack. Doses must be taken continuously at the same time each day. Refer to individual product guidelines on how to manage missed doses and for detailed dosing instructions.
Oral Dysfunctional uterine bleeding
Adult: As norethisterone base: Treatment: 5 mg tid for 10 days. Prophylaxis of recurrence: 5 mg bid from day 19 to day 26 of the menstrual cycle. As norethisterone acetate: 2.5-10 mg daily for 5-10 days. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Postponement of menstruation
Adult: As norethisterone base: 5 mg tid, starting 3 days before the expected onset of menstrual cycle.
Oral Premenstrual syndrome
Adult: As norethisterone base: 5 mg daily from day 16 to day 25 of the menstrual cycle. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
What are the brands available for Norethisterone in Malaysia?
Known, suspected, or history of breast, genital or hormone-dependent cancer; untreated endometrial hyperplasia, undiagnosed abnormal vaginal bleeding; previous idiopathic, history or current VTE (e.g. deep vein thrombosis, pulmonary embolism); active or recent arterial thromboembolic disease (e.g. stroke, MI) or any prodromal symptoms (e.g. transient ischaemic attack, angina pectoris); porphyria; history of idiopathic jaundice, severe pruritus or pemphigoid gestationis during pregnancy; Dubin-Johnson syndrome, Rotor syndrome, active or history of liver tumuors; severe diabetes with vascular changes, pathologically increased blood pressure (as norethisterone enantate). Hepatic disease or impairment. Pregnancy. Contraindications may vary among individual products and countries (refer to specific product guidelines).
Special Precautions
Patient with hyperlipidaemia, risk factors for CV disease (e.g. hypercholesterolaemia, diabetes mellitus, hypertension, obesity, SLE, increasing age); predisposition for breast cancer (e.g. family history, presence of susceptibility genes [e.g. BRCA1, BRCA2]); diseases that may be exacerbated by fluid retention (e.g. migraine, asthma, epilepsy); depression; history of chloasma gravidarum. Smokers. Patients undergoing surgery or those who experience prolonged immobilisation. Norethisterone is available in different salt forms with varying dosing instructions; different formulations of some products may not be equivalent and are not interchangeable (refer to specific product information). Renal impairment. Lactation.
Adverse Reactions
Significant: Delayed follicular atresia, ovarian cysts, ectopic pregnancy; menstrual bleeding irregularities (e.g. shortened or prolonged menstrual cycles, amenorrhoea, breakthrough bleeding, spotting); may increase the risk of thromboembolic diseases; fluid retention, significant blood pressure elevation, jaundice, hepatitis; visual abnormalities, including partial or complete loss of vision, proptosis, diplopia, papilloedema, or retinal vascular lesions; new-onset or aggravation of migraine; mood changes, depression; chloasma, decreased glucose tolerance, changes in lipid metabolism (e.g. altered serum lipid profile). Rarely, malignant or benign hepatic tumours. Cardiac disorders: Palpitations, tachycardia. Gastrointestinal disorders: Nausea, vomiting, bloating. General disorders and administration site conditions: Fatigue; inj site reactions (IM). Immune system disorders: Hypersensitivity reactions. Investigations: Abnormal LFT, weight gain. Metabolism and nutrition disorders: Oedema, changes in appetite. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Insomnia, nervousness. Reproductive system and breast disorders: Abnormal uterine bleeding, changes in cervical secretions, cervical erosion, breast tenderness or discomfort, mastalgia, changes in libido. Skin and subcutaneous tissue disorders: Rash, acne, pruritus, urticaria, alopecia. Potentially Fatal: Rarely, increased risk of intra-abdominal haemorrhage associated with ruptured hepatic adenoma.
IM/Parenteral/PO/Transdermal: Z (Congenital malformations and masculinisation of the female foetus have been reported. Contraindicated.)
Monitoring Parameters
Evaluate pregnancy status before treatment initiation, if 2 consecutive menstrual cycles are missed, or if the menstrual cycle is delayed and ≥1 tab was taken late or missed in a cycle wherein intercourse has occurred (without the use of back-up contraception). Perform physical examination regularly, including blood pressure monitoring, breast and pelvic examination, and Papanicolaou smear. Monitor weight, health status changes, glycaemic control (in diabetic patients), and lipid profile (in hyperlipidaemic patients). Perform endometrial sampling as necessary to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding. Assess for signs and symptoms of thromboembolic disorders, changes in vision and depression.
Overdosage
Symptoms: Nausea, vomiting, vaginal bleeding, and breast enlargement. Management: Symptomatic treatment. May perform gastric lavage within 4 hours of ingestion or if the dose ingested is large.
Drug Interactions
May reduce the therapeutic effect with anticonvulsants (e.g. phenobarbital, carbamazepine, phenytoin, felbamate), phenylbutazone, rifampicin, rifabutin, nevirapine, efavirenz, tetracycline, ampicillin, oxacillin, sulfamethoxazole + trimethoprim, and griseofulvin. May increase the serum concentrations of ciclosporin, prednisone, prednisolone, cloprednol and other corticosteroids. Plasma concentration may be increased with strong CYP3A4 inhibitors (e.g. ketoconazole).
Food Interaction
May result in decreased contraceptive effect with St. John's wort.
Lab Interference
Decreased response to metyrapone test. May interfere with the results of tests for coagulation factors, lipids, glucose tolerance, thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin.
Action
Description: Mechanism of Action: Norethisterone is a progestogen that acts on the endometrium by converting the estrogen-induced proliferative phase to the secretory phase. It blocks the secretion of pituitary gonadotropins, thereby preventing follicular maturation and ovulation. Additionally, norethisterone increases the protein and sialic acid content of cervical mucus (causing it to thicken) and changes the structure of endometrium, resulting in inhibited sperm penetration and impaired implantation, respectively. Synonym(s): Norethindrone. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Completely absorbed after IM inj. Bioavailability: 4%. Time to peak plasma concentration: 1-3 hours. Distribution: Enters breast milk (small amounts). Volume of distribution: Approx 4 L/kg. Plasma protein binding: 61% to albumin; approx 36% to sex hormone-binding globulin. Metabolism: Metabolised mainly in the liver; undergoes first-pass metabolism. Norethisterone acetate is deacetylated to norethisterone which further undergoes hepatic reduction and conjugation into glucuronide and sulfide conjugates. Norethisterone enantate is metabolised via enzymatic hydrolysis into norethisterone and heptanoic acid. Norethisterone is also partly metabolised to form ethinylestradiol. Excretion: Via urine (50-80% as metabolites); faeces (20-40% as metabolites). Elimination half-life: 8-9 hours.
Chemical Structure
Norethisterone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6230, Norethindrone. https://pubchem.ncbi.nlm.nih.gov/compound/Norethindrone. Accessed Mar. 26, 2025.
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
Bayer New Zealand Limited. Primolut N 5 mg Tablets data sheet 05 June 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 18/02/2025.Brayfield A, Cadart C (eds). Norethisterone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/02/2025.Depocon Injection (Duopharma [M] Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 18/02/2025.Gallifrey Tablet (Xiromed LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 18/02/2025.Joint Formulary Committee. Norethisterone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 24/03/2025.Norethindrone Acetate. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 24/03/2025.Norethisterone 5 mg Tablets (Wockhardt UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 24/03/2025.Norethisterone [Norethindrone]. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 18/02/2025.Noriday 350 microgram Tablets (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 18/02/2025.Noriday 350 microgram Tablets (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 18/02/2025.Noristerat 200 mg Solution for Intramuscular Injection (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 18/02/2025.Normens 5 mg Tablet (Vitamode Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 18/02/2025.Orquidea Tablet (Xiromed, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 18/02/2025.Pfizer New Zealand Limited. Noriday 28 Day 0.35 mg Tablets data sheet 12 January 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 18/02/2025.Sunolut Tablet 5 mg (Sunward Pharmaceutical Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 18/02/2025.
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