Norethisterone

Registered South African indications;

• Dysfunctional uterine bleeding
• Amenorrhoea
• Endometriosis
• Postponement of menstruation

Contraindications

• Hypersensitivity to the active substance or to any of the excipients
• Known or suspected pregnancy
• Lactation
• Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g., deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident
• Presence of a history of prodromi of a thrombosis (e.g., transient ischaemic attack, angina pectoris)
• A high risk of venous or arterial thrombosis
• History of migraine with focal neurological symptoms
• Diabetes mellitus with vascular involvement
• Presence or history of severe hepatic disease, as long as liver function values have not returned to normal
• Use of direct-acting antiviral (DAA) medicines containing ombitasvir, paritaprevir, or dasabuvir, and combinations of these
• Presence or history of liver tumours (benign or malignant)
• Known or suspected sex hormone-dependent malignancies

Cautions

• Renal impairment
• Migraine or severe headaches
• Hypertension
• Circulatory disorders
• Hyperlipidaemias
• Diabets mellitus
• Risk factors for venous thromboembolism
• Chloasma
• Depression
• Visual abnormalities
• Epilepsy
• Asthma
• Smoking
• Breast cancer
• Cervical cancer
• Angioedema 
• Persistent HPV infection
• Crohn's disease
• Ulcerative colitis
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Dysfunctional uterine bleeding - acute management

• Oral (tab): 5mg, 4hrly; Treatment duration: 48hrs

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Once bleeding has stopped, use combined oral contraceptive (1 tablet, 8hrly) for 7 days 

Withdrawal bleeding resembling a normal period can be expected within 2-4 days after completion of treatment course; After withdrawal bleeding, use combined oral contraceptive (1 tablet, dly) for 3-6 cycles OR prophylactic dose of norethisterone (see below)

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If haemorrhage is not arrested by the above treatment course, further investigation is required

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Dysfunctional uterine bleeding - prophylaxis of recurrence

• Oral (tab): 15mg, dly on day 5-26 of menstrual cycle; Treatment duration: 3-6 cycles following on from acute treatment of dysfunctional uterine bleeding

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1st day of menstruation = 1st day of cycle

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Relief of amenorrhoea

Initial

• Oral (tab): 5mg, 8-12hrly on day 19-26 of cycle

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Combine with estrogen treatment (estradiol valerate): IM: 10mg, on day 1 and day 14 of cycle (1st day of cycle = day that oestrogen given)

Withdrawal bleeding expected on day 28

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Maintenance:

• Oral (tab): 5mg, 8-12hrly on day 19-26 of cycle; Treatment duration: at least 2-3 cycles

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Combined with estrogen treatment (estradiol valerate): IM: 10mg, on day 6 and day 16 of menstrual cycle (1st day of menstruation/withdrawal bleeding = 1st day of cycle)

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In the case of secondary amenorrhoea, commence treatment with norethisterone at the earliest 8 weeks after the last menstrual period

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Practice contraception with non-hormonal methods during course of treatment

If withdrawal bleeding fails to occur at regular 28 day intervals, the possibility of pregnancy must be investigated

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After maintenance treatment for 2-3 cycles, an attempt can be made to stop the oestrogen and maintain the cycle purely on cyclical norethistrerone

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Prementrual tension and cyclical mastopathy

• Oral (tab): 5mg, 8-24hrly on day 19-26 of menstrual cycle

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Practice contraception with non-hormonal methods during course of treatmen

If withdrawal bleeding fails to occur at regular 28 day intervals, the possibility of pregnancy must be investigated

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Endometriosis

• Oral (tab): 5mg, 12hrly; Treatment duration: at least 4-6 months

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Initiate on day 5 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

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During treatment ovulation and menstruation will not occur

If breakthrough bleeding occurs, increase dose temporarily to 10mg, 12hrly; Resume dose of 5mg, 12hrly once bleeding stops

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Postponement of menstruation

• Oral (tab): 5mg, 8hrly, initiated 3 days before expected menstruation; Max duration of treatment: 10-14 days

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If withdrawal bleeding does not occur 2-3 days after cessation of norethisterone, the possibility of pregnancy must be investigated

Not indicated for use in children

Pregnancy

• Contraindicated
• Norethisterone is contraindicated in women with suspected pregnancy. Several reports suggest an association between foetal exposure to female sex hormones, including oral contraceptives, and congenital anomalies

Breastfeeding

• Contraindicated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated
  Presence or history of severe hepatic disease, as long as liver function values have not returned to normal

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Migraine
• Dizziness
• Depression

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Nausea
• Abdominal pain

Hepatobiliary Disorders

• Cholestasis
• Jaundice

Genitourinary Disorders

• Uterine/ vaginal bleeding 
• Hypomenorrhoea
• Amenorrhoea

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Oedema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

Sensory Disorders

• Visual disturbances

• CYP450 inducers
• St. Johns wort
• Interference with certain laboratory tests  

• Gynaecological examination
• Cervical cytology
• Breast examination
• Blood pressure

Specific cases may require

• Serum glucose 
• Lipid profiles 

Norethisterone has progestational actions similar to those of progesterone, but is a more potent inhibitor of ovulation and has weak oestrogenic and androgenic properties. It has an inhibitory effect on the secretion of gonadotropins in the anterior lobe of the pituitary, thereby preventing ovulation. Norethisterone also has a styptic effect: a local influence on the endometrium leading to the cessation of dysfunctional bleeding.

Tablet 5mg

Primolut N (Bayer) originator

COMBINATION PREPARATIONS

Oestradiol valerate/ Norethisterone

Tablet 1mg/0.5mg

• Activelle (Novo Nordisk) originator

Tablet 1mg/1mg

• Estro-Pause N (Adcock)
• Novofem (Novo Nordisk) originator

Oestradiol valerate/ Norethisterone

Tablet 2mg/2mg

• Estro-Pause N Forte (Adcock)
• Kilogest (Novo Nordisk) originator

Tablet 2mg/1mg

• Trisequence  (Novo Nordisk) originator

Tablet 4mg/1mg

• Trisequence Forte (Novo Nordisk) originator