Norethisterone Tablets BP 5mg

1. Name Of The Medicinal Product

NORETHISTERONE TABLETS BP 5MG

2. Qualitative And Quantitative Composition

Each tablet contains 5mg of Norethisterone.

3. Pharmaceutical Form

Tablet.

4. Clinical Particulars

4.1 Therapeutic Indications

1. Metropathia haemorrhagica.

2. Premenstrual syndrome.

3. Postponement of menstruation.

4. Dysmenorrhoea.

5. Endometriosis.

6. Menorrhagia.

7. Disseminated Carcinoma of the breast

4.2 Posology And Method Of Administration

Posology

1. Metropathia haemorrhagica (dysfunctional uterine bleeding): 1 tablet 3 times daily for 10 days. Bleeding is arrested usually within 1-3 days. A withdrawal bleeding resembling normal menstruation occurs within 2-4 days after discontinuing treatment.

Prophylaxis against 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 1 tablet twice daily from the 19th to the 26th day of the cycle.

2. Premenstrual syndrome (including premenstrual mastalgia): Premenstrual symptoms such as headache, migraine, breast discomfort, water retention, tachycardia and psychic disturbances may be relieved by the administration of 2-3 tablets 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 (eg operations, travel, sports) Dosage: 1 tablet three times daily, starting 3 days before the expected onset of menstruation. A normal period should occur 2-3 days after the patient has stopped taking tablets.

4. Dysmenorrhoea: functional or primary dysmenorrhoea is almost invariably relieved by the suppression of ovulation. 1 tablet three times daily for 20 days, starting on the fifth day of the cycle (the first day of menstruation counting as day 1). 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 5th day of the cycle with 2 tablets daily for the first few weeks. In the event of spotting, the dosage is increased to 4 and, if necessary, 5 tablets daily.

After bleeding has ceased, the initial dose is usually sufficient. Duration of treatment: 4-6 months continuously, or longer if necessary.

6. Menorrhagia (hypermenorrhoea): 1 tablet 2-3 times a day from the 19th to the 26th day of the cycle (counting the first day of menstruation as day 1).

7. Disseminated Carcinoma: of the breast the starting dose is 8 tablets per day increasing to 12 tablets after 6 weeks if no regression is noted and may be continued indefinitely. If no remission is obtained within 9 weeks of treatment none should be expected.

Not intended for use in children.

Not intended for elderly patients.

Method of Adminstration

For oral use.

4.3 Contraindications

• Hypersensitivity to norethisterone or any of the other ingredients in the tablet

• Pregnancy.

• Disturbance of liver function.

• Dubin-Johnson and Rotor Syndromes.

• History during pregnancy of idiopathic jaundice.

• Severe pruritis

• Herpes gestationis.

• Undiagnosed irregular vaginal bleeding.

• Previous idiopathic or current thromboembolism (deep vein thrombosis, pulmonary embolism).

• Active or recent arterial thromboembolic disease (eg. angina, myocardial infarction).

• Porphyria.

• Breast or genital tract carcinoma, unless norethisterone is being used as part of the management of these conditions.

• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.4 Special Warnings And Precautions For Use

The possibility of pregnancy must be excluded if menstrual bleeding does not occur following a course of Norethisterone before commencement of a further episode of therapy.

Treatment should be discontinued if the following occur:

Jaundice or deterioration in liver function

Significant increase in blood pressure

New onset of migraine-type headaches

Progesterones may cause fluid retention. Special care should be taken when prescribing Norethisterone for patients with conditions that may be aggravated by this factor:

Epilepsy

Migraine

Asthma

Cardiac dysfunction

Renal dysfunction

Diabetes Mellitus

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

• The effects of Norethisterone will be altered if other sex hormones are prescribed simultaneously.

• The metabolism of progestogens may be increased by concommitant administration of compounds known to induce drug-metabolising enzymes, especially 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 co-trimoxazole)

• Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibits inducing propoerties when used concomitantly with steroid hormones.

• Herbal preparations containing St John's Wort (Hypericum Perforatum) may induce the metabolism of progestogens, therefore progestogen levels may be reduced.

• Aminoglutethimide has been reported to decrease plasma of levels of some progestogens.

• Concurrent administration of ciclosporin and norethisterone has been reported to lead to increased plasma ciclosporin and/or decrease plasma norethisterone levels.

• Care should be taken when progestogens are administered with other medicines which also cause fluid retention, for example NSAIDs and vasodilators.

Other forms of interactions:

Progestogens can influence certain laboratory tests (e.g. tests for hepatic function, thyroid function, coagulation, dextrose, cortisol, gonadotropin, testosterone, progesterone and oestrogen).

4.6 Pregnancy And Lactation

Norethisterone is contraindicated in pregnancy, and should be avoided during lactation as it is present in breast milk.

4.7 Effects On Ability To Drive And Use Machines

Patients should be cautioned about the possibility of dizziness, drowsiness and visual changes and informed of its significance in the driving of vehicles and the operation of machinery.

4.8 Undesirable Effects

Side effects rarely occur in doses of 15mg daily. Progestogens given alone at low doses have been associated with the following undesirable effects

• Genitourinary: breakthrough bleeding , spotting, amenorrhoea, abnormal bleeding (irregular, increase or decrease), alterations of cervical secretions, cervical erosions, prolonged anovulation.

Breast galactorrhoea, mastodynia, tenderness.

• Gastrointestinal: nausea, vomiting.

• Cardiovascular: thrombo-embolic disorders, increased blood pressure, pulmonary embolism, retinal thrombosis, thrombophlebitis.

• Hepatobiliary: cholestatic liver changes, disturbed liver function.

• Neurological and Special Senses: depression, headache, dizziness, fatigue, insomnia, nervousness, drowsiness, loss of concentration, vision disorders and intolerance to contact lenses.

• Metabolic and Nutritional: altered serum lipid and lipoprotein profiles, incresed fasting insulin levels, decreased glucose tolerance, diabetic cataract, exacerbation of diabetes mellitus, glyosuria.

• Skin and Mucous membranes: acne, hirsutism, alopecia, rash, uticaria, exacerbation of existing skin conditions.

• Hypersensitivity reactions: (e.g. anaphylaxis and anaphylactoid reactions, angioedema).

• Miscellaneous: oedema, fluid retention, bloating, weight gain, fever, change in appetite, deepening of the voice, change in libido.

4.9 Overdose

Overdosage may present as nausea, vomiting, breast enlargement and later vaginal bleeding. There is no specific antidote and treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code: G03DC02

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.

In carcinoma norethisterone may act by pituitary inhibition by an anti-oestrogenic effect or by direct action on the tumour. The mode of action is not fully understood.

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 1-2½ 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 5 to 12 hours, with a mean of 7.6 hours. After 24 hours plasma levels are generally about 1% of peak concentration. Approximately 60% of the administered dose is excreted as metabolites in the urine and faeces.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The tablets also contain: lactose, maize starch and magnesium stearate.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf-life

60 Months.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special Precautions For Storage

Do not store above 25°C.

Store in the original package.

6.5 Nature And Contents Of Container

1. Opaque plastic containers with press-on tamper-evident lid.

2. Blister pack of PVC and aluminium foil.

Pack sizes: 100's, 500's (Opaque plastic container)

Pack sizes: 30's, 72's, 180's (Blister pack)

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Actavis UK Limited (Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0483

9. Date Of First Authorisation/Renewal Of The Authorisation

4.8.99

10. Date Of Revision Of The Text

10.07.09