Norethisterone 5mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Norethisterone 5mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Norethisterone 5.0mg For excipients, see 6.1
3 PHARMACEUTICAL FORM
Tablet.
Norethisterone 5mg Tablets are 6.5mm, round, white, uncoated tablets with “NE 5” on one side and a break line on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Norethisterone has the following clinical indications:
At low dose:
Metropathia haemorrhagica Pre-menstrual syndrome Postponement of menstruation Dysmenorrhoea Endometriosis Menorrhagia
At high dose:
Disseminated carcinoma of the breast
4.2 Posology and method of administration
For oral administration
Low dose
1. Metropathia haemorrhagica (dysfunctional uterine bleeding): 5mg three times daily for ten days. Bleeding is arrested usually within one to three days. A withdrawal bleeding resembling normal menstruation occurs within two to four days after discontinuing treatment.
Prophylaxis of recurrence of dysfunctional bleeding: if there are no signs of resumption of normal ovarian function (no rise of morning temperature in the second half of the cycle), recurrence must be anticipated. Cyclical bleeding can be established with 5mg twice daily from the 19th to the 26th day of the cycle.
2. Pre-menstrual syndrome (including pre-menstrual mastalgia): Pre-menstrual symptoms such as headache, migraine, breast discomfort, water retention, tachycardia and psychic disturbances may be relieved by the administration of 10 - 15mg daily from the 19th to the 26th day of the cycle. Treatment should be repeated for several cycles. When treatment is stopped, the patient may remain symptom free for a number of months.
3. Postponement of menstruation: In cases of too frequent menstrual bleeding, and in special circumstances (e.g. operations, travel, sports) 5mg three times daily, starting three days before the expected onset of menstruation. A normal period should occur two to three days after the patient has stopped taking tablets.
4. Dysmenorrhoea: Functional or primary dysmenorrhoea is almost invariably relieved by the suppression of ovulation. 5mg three times daily for 20 days, starting on the fifth day of the cycle (the first day of menstruation counting as day one). Treatment should be maintained for three to four cycles followed by treatment-free cycles. A further course of therapy may be employed if symptoms return.
5. Endometriosis (pseudo-pregnancy therapy): long-term treatment is commenced on the fifth day of the cycle with 10mg daily for the first few weeks. In the event of spotting, the dosage is increased to 20mg and, if necessary, 25mg daily.
After bleeding has ceased, the initial dose is usually sufficient. Duration of treatment: four to six months continuously, or longer if necessary.
6. Menorrhagia (hypermenorrhoea): 5mg two to three times a day from the 19th to the 26th day of the cycle (counting the first day of menstruation as day one).
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.
Not for use in children.
Not for elderly patients.
Contraindications
4.3
Known hypersensitivity to Norethisterone or any of the excipients. Pregnancy. Hepatic impairment or hepatic disease. History during pregnancy of: idiopathic jaundice, severe pruritus, or pemphigoid gestationis. History of breast cancer. Active trophoblastic disease (until return to normal of urine- and plasma-gonadotrophin concentration) - seek specialist advice. Patients should not use norethisterone after a recent evacuation of a hydatiform mole. Undiagnosed vaginal bleeding. History or current high risk of arterial disease. Breast or genital tract carcinoma, unless norethisterone is being used as part of the management of these conditions.
Porphyria. Hepatic tumour or a history of hepatic tumour. Patients with previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism).
4.4 Special warnings and precautions for use
Progestogens may cause fluid retention and should be used with caution in conditions that may worsen with fluid retention:
• Epilepsy
• Asthma
• Migraine
• Hypertension
• Cardiac or renal disease
• Other conditions which may be aggravated by fluid retention Norethisterone should be used with care in patients with:
• Liver disturbances including recurrent cholestatic jaundice. Alterations in liver function have been reported.
• History of depression
• Diabetes mellitus or decreased glucose tolerance
Therapy should be discontinued if the following occurs:
- Jaundice or deterioration in liver function.
- New onset of migraine
- Significant increase in blood pressure
If menstrual bleeding should fail to follow a course of treatment, the possibility of pregnancy should be excluded before a further course of treatment is given.
Norethisterone should be used in caution in women with a history of ectopic preganancy.
Progestogens should be used with caution in women with functional ovarian cysts
There is a small increase in the risk of having breast cancer diagnosed
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 VTE, although the role of progestogens is uncertain.
Generally recognised risk factors for VTE include a personal or family history, and severe obesity (BMI>30kg.m2). In women with these risk factors the benefits of treatment need to be carefully weighed against the risks. There is no consensus about the possible role of varicose veins in VTE.
The risk of VTE may be temporarily increased by 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 four to six weeks pre-operatively.
If VTE develops after initiating therapy, the drug should be discontinued.
Progestogens should be used with caution in those susceptible to thromboembolism, particularly with high doses.
Progestogens can decrease glucose tolerance and patients should be monitored
closely
Progestogens should be used in caution with patients with malabsorption syndromes.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Antidepressants: St John’s wort may reduce serum levels of progestogens by enhancing their metabolism.
Anticoagulants: Progestogens may enhance or reduce anticoagulant effect of coumarins and antagonise anticoagulant effect of pheninidione.
Antidiabetics: norethisterone may antagonise the effects of antidiabetics.
Antidepressants: Concomitant use of St. John’s wort with progesterone should be avoided.
Antiepileptics: Hepatic enzyme-inducing antiepileptic drugs, e.g. eslicarbazepine, rufinamide, carbamazepine, oxcarbazepine, phenytoin, topiramate and barbiturates (including phenobarbital and primidone) may enhance the metabolism of progestogens. Norethisterone may reduce lamotrigine plasma concentration.
Antifungals: The effect of norethisterone may be reduced by griseofulvin, possibly by accelerated metabolism of the progestogen.
Antituberculous drugs: Rifamycins may accelerate metabolism of progestogens.
Antiviral drugs: Nevirapine, nelfinavir or ritonavir may accelerate metabolism of norethisterone. Norethisterone plasma concentration increased with concomitant administration of amprenavir. Amprenavir plasma concentration decreased with concomitant administration of norethisterone.
Dopaminergics: Progestogens increase plasma concentration of selegiline (with an increased risk of toxicity)
Drugs for reversal of neuromuscular blockade: Plasma concentrations of progestogens possibily reduced with the use of sugammadex.
Immunosuppressants: ciclosporin. Metabolism is inhibited by progestogens.
Lipid regulating drugs: Atorvastatin increases plasma concentration of norethisterone.
Muscle relaxants: Progestogens possibly increase plasma concentration of tizanidine (with an increased risk of toxicity)
Vasodilator antihypertensives: Sitaxentan increases plasma concentration of progestogens.
Cytochrome P450 hepatic enzymes are those enzymes of concern, which may be affected by drug interaction resulting in either induction or inhibition of drug metabolism.
4.6 Fertility, pregnancy and lactation
Norethisterone is contraindicated in pregnancy, and should be avoided during lactation, as it is present in breast milk.
Hypospadias in males and virilisation of females has been reported in the offspring of mothers who have taken norethisterone during pregnancy.
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
Side-effects rarely occur with doses of 15mg daily.
Gastrointestinal disorders: gingival inflammation, nausea, abdominal pain and vomiting,
General: fatigue, drowsiness or insomnia, headache, fever, dizziness
Hepato-biliary disorders: alterations in liver function have been reported and jaundice has been reported rarely.
Immune system disorders: anaphylaxis or anaphylactoid reactions may occur rarely; allergic skin rashes.
Psychiatric disorders: depression and nervousness.
Metabolism and nutrition disorders: hyperglycaemia, changes in appetite or weight gain, oedema and fluid retention, hypercalcaemia, hyperinsulinaemia, and the potential for changes in serum lipid and lipoprotein concentrations to occur with noterthisterone.
Nervous system disorders: exacerbation of epilepsy and migraine.
Ophthalmic disorders: intolerance to contact lenses and deterioration in vision in patients who are short sighted has been reported with the use of the combined oral contraceptive pill and may be applicable to this product.
Reproductive disorders: The commonest side-effect is breakthrough bleeding, particularly when treatment is continuous over a long period. Other menstrual irregularities may occur, including amenorrhoea, spotting and menorrhagia. .Breast changes, including discomfort; ovarian cysts; changes in libido; pre-menstrual syndrome like symptoms; Androgenic effects with hirsutism and oestrogenic effects have been reported after prolonged therapy. There is a small increase in the risk of having breast cancer diagnosed.
Vascular disorders: Rarely, thromboembolic events with high doses. Hypertension can potentially occur with norethisterone.
Skin and subcutaneous tissue disorders: acne, alopecia, allergic skin rashes, urticaria, pruritus, and melasma or chloasma.
4.9 Overdose
There are no reports of ill-effects from overdose.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Norethisterone is a synthetic, potent, orally active progestogen which, by virtue of its progestogenic effects, produces secretory effects on oestrogen-primed genital tissue, has a sedative effect on uterine muscle and a styptic effect on uterine haemorrhage.
Norethisterone also has some androgenic effects and some weak oestrogenic activity.
5.2 Pharmacokinetic properties
Norethisterone when given orally is well absorbed from the gastrointestinal tract, with peak plasma concentrations (which may be dose dependent) generally occurring within one to two and a half-hours.
Bioavailability of norethisterone is variable, probably due to first pass effects in gut wall or liver, which may be influenced by many factors including hormonal status, diet and exercise.
Plasma half-life after a dose of 5mg is of the order of five hours. After 24 hours plasma levels are generally about 1% of peak concentration.
5.3 Preclinical safety data
There are no pre-clinical data of any relevance to the prescriber which are additional to those already included in other sections.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Starch Maize Magnesium Stearate
6.2 Incompatibilities
None.
6.3 Shelf life
Five years.
6.4 Special precautions for storage
Do not store above 25 °C.
Store in the original package.
6.5 Nature and contents of container
Opaque plastic tablet containers with press-on tamper evident lid containing 100 and 500 tablets.
Blister pack of PVC and aluminium foil containing 30, 72 and 180 tablets.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF UK.
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0152
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/03/2009
10 DATE OF REVISION OF THE TEXT
14/05/2013