Active Ingredient:
norethisterone
Company:
Wockhardt
ATC code:
L02AB
Prescription only medicine
Tablet.
Norethisterone 5mg Tablets are 6.5mm, round, white, uncoated tablets with “NE 5” on one side and a break line on the other.
Therapeutic indications
At low dose:
Dysfuntional uterine bleeding
Polymenorrhoea
Menorrhagia
Metropathia
Haemorrhagia
Pre-menstrual syndrome
Postponement of menstruation
At high dose:
Disseminated carcinoma of the breast.
Posology
Low dose
Posology and method of administration
Dysfunctional uterine bleeding, polymenorrhoea, menorrhagia, dysmenorrhoea and metropathia haemorrhagia: 1 tablet three times daily for 10 days; bleeding usually stops within 48 hours. Withdrawal bleeding resembling true menstruation occurs a few days after the end of treatment. One tablet twice daily, from days 19 to 26 of the two subsequent cycles, should be given to prevent recurrence of the condition.
Endometriosis: 1 tablet three times daily for a minimum treatment period of six months. The dosage should be increased to 4 or 5 tablets a day if spotting occurs. The initial dosage should be resumed when bleeding or spotting stops.
Postponement of menstruation: 1 tablet three times daily, starting three days before the expected onset of menstruation. Menstruation usually follows within three days of finishing the treatment.
Pre-menstrual syndrome: 1 tablet daily from days 16 to 25 of the menstrual cycle.
High dose
For disseminated breast carcinoma the starting dose is 8 tablets (40mg) per day increasing to 12 tablets (60mg) if no regression is noted.
Method of administration
Oral Administration
Contraindications
Hypersensitivity to the active substance or any of the excipients listed in section 6.1
Pregnancy
Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism)
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
Disturbance of liver function
History during pregnancy of idiopathic jaundice
Severe pruritus or pemphigoid gestationis
Undiagnosed irregular vaginal bleeding
Porphyria
Special warnings and precautions for use
If menstrual bleeding should fail to follow a course of Utovlan, the possibility of pregnancy must be excluded before a further course is given.
Therapy should be discontinued if the following occur:
– Jaundice or deterioration in liver function
– Significant increase in blood pressure
– New onset of migraine-type headache
Progestogens may cause fluid retention. Special care should be taken when prescribing norethisterone in patients with conditions which might be aggravated by this factor:
– Epilepsy
– Migraine
– Asthma
– Cardiac dysfunction
– Renal dysfunction
Risk of venous thromboembolism (VTE)
Long term use of low dose progestogens as part of combined oral contraception or combined hormone replacement therapy has been associated with an increased risk of venous thromboembolism, although the role of progestogens in this aetiology is uncertain. A patient who develops symptoms suggestive of thromboembolic complications should have her status and need for treatment carefully assessed before continuing therapy.
Any patient who develops an acute impairment of vision, proptosis, diplopia or migraine headache should be carefully evaluated ophthalmologically to exclude papilloedema or retinal vascular lesions before continuing medication.
Generally recognised risk factors for VTE include a personal history or family history, severe obesity (BMI >30 kg/m2) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.
Treatment with steroid hormones may add to these risk factors. Personal or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophillic predisposition. Until a thorough evaluation of thrombophillic factors has been made or anticoagulant treatment initiated, use of progestogens in these patients should be viewed as contraindicated. Where a patient is already taking anticoagulants, the risks and benefits of progestogen therapy should be carefully considered.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all post-operative patients, scrupulous attention should be given to prophylactic measures to prevent VTE. Where prolonged immobilisation is likely to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to stopping progestogen therapy 4-6 weeks pre-operatively. Treatment should not be restarted until the patient is fully remobilised.
If VTE develops after initiating therapy the drug should be withdrawn. Patients should be advised to contact their doctor immediately if they become aware of a potential thromboembolic symptom (e.g., painful swelling in the leg, sudden pain in the chest, dyspnoea).
Interaction with other medicinal products and other forms of interaction
Interaction with other medicines
The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes. These compounds include anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g., rifampicin, rifabutin, nevirapine, efavirenz, tetracyclines, ampicillin, oxacillin and cotrimoxazole)
Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John’s wort (Hypericum perforatum) may induce the metabolism of progestogens. Progestogen levels may therefore be reduced.
Aminoglutethimide has been reported to decrease plasma levels of some progestogens.
Concurrent administration of cyclosporin and norethisterone has been reported to lead to increased plasma cyclosporin levels and/or decreased plasma norethisterone levels.
When used in combination with cytotoxic drugs, it is possible that progestogens may reduce the haematological toxicity of chemotherapy.
Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.
Other forms of interaction
Progestogens can influence certain laboratory tests (e.g., tests for hepatic function, thyroid function and coagulation).
Fertility, pregnancy and lactation
Norethisterone is contraindicated in pregnancy
Undesirable effects
Progestogens given alone at low doses have been associated with the following undesirable effects:
| Genitourinary | breakthrough bleeding, spotting, amenorrhoea, abnormal uterine bleeding, (irregular, increase, decrease), alterations of cervical secretions, cervical erosions, prolonged anovulation |
| Breast | galactorrhoea, mastodynia, tenderness |
| Central Nervous System | depression, headache, dizziness, fatigue, insomnia, nervousness, somnolence, confusion, euphoria, loss of concentration, vision disorders |
| Gastrointestinal/Hepatobiliary | nausea, vomiting, cholestatic icterus/jaundice, constipation, diarrhoea, dry mouth, disturbed liver function |
| Metabolic & Nutritional | altered serum lipid and lipoprotein profiles, increased fasting glucose levels, increased fasting insulin levels, decreased glucose tolerance, adrenergic-like effects (e.g., fine hand tremors, sweating, cramps in calves at night), corticoid-like effects (e.g., Cushingoid syndrome), diabetic cataract, exacerbation of diabetes mellitus, glycosuria |
| Cardiovascular | thrombo-embolic disorders, cerebral and myocardial infarction, congestive heart failure, increased blood pressure, palpitations, pulmonary embolism, retinal thrombosis, tachycardia, thrombophlebitis |
| Skin & Mucous Membranes | acne, hirsutism, alopecia, pruritis, rash, urticaria |
| Allergy | hypersensitivity reactions (e.g., anaphylaxis & anaphylactoid reactions, angioedema) |
| Miscellaneous | oedema/fluid retention, bloating, weight gain, pyrexia, change in appetite, change in libido, hypercalcaemia, malaise |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Overdose
Overdosage may be manifested by nausea, vomiting, breast enlargement and later vaginal bleeding. There is no specific antidote and treatment should be symptomatic.
Gastric lavage may be employed if the overdosage is large and the patient is seen sufficiently early (within four hours).