NAME OF THE MEDICINAL PRODUCT
Norethisterone 5mg tablet
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5mg norethisterone.
Excipient(s) with known effect
Each tablet contains 62.25 mg lactose (as monohydrate)
Tablet. Norethisterone 5mg Tablets are 6.5mm, round, white, uncoated tablets with “NE 5” on one side and a break line on the other.
At low dose:
Dysfuntional uterine bleeding
Postponement of menstruation
At high dose:
Disseminated carcinoma of the breast.
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.
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
Hypersensitivity to the active substance or any of the excipients listed in section 6.1
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
SPECIAL PRECAUTIONS & WARNINGS
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:
– 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 lactationNorethisterone is contraindicated in pregnancy
Effects on ability to drive and use machines
Norethisterone has no influence on the ability to drive and use machines.
|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|
Progestogens given alone at low doses have been associated with the following undesirable effects:
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.
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).
Pharmotherapeutic group (ATC code) L02A B.
Norethisterone given at intermediate doses (5-10mg) suppresses ovulation via its effect on the pituitary. The endogenous production of oestrogens and progesterones are also suppressed, and the ectopic endometrium is converted to a decidua resembling that of pregnancy. In carcinoma norethisterone may act by pituitary inhibition or by direct action on tumour deposits.
Norethisterone is rapidly and completely absorbed after oral administration, peak plasma concentration occurring in the majority of subjects between 1 and 3 hours. Due to first-pass metabolism, blood levels after oral administration are 60% of those after i.v. administration. The half life of elimination varies from 5 to 12 hours, with a mean of 7.6 hours. Norethisterone is metabolised mainly in the liver. Approximately 60% of the administered dose is excreted as metabolites in urine and faeces.
Preclinical safety data
The toxicity of norethisterone is very low. Reports of teratogenic effects in animals are uncommon. No carcinogenic effects have been found even in long-term studies.
List of excipients
Special precautions for storage
Do not store above 25°C.
Store in original packaging in order to protect from light.
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.
Not all pack sizes may be marketed.
Special precautions for disposal and other handling
No special requirements.
MARKETING AUTHORISATION HOLDER
TAJ PHARMA CIS LTD.
Marksistsky lane 6, office 221, Moscow, 109147, Russia
Manufactured in India by:
TAJ PHARMACEUTICALS LTD,
220, Mahagujarat Ind. Estate, Moraiya,
Tal. Sanand , Dist. Ahmedabad,
What is in this leaflet
- What Norethisterone is and what is it used for
2. What do you need to know Before you take Norethisterone
3. How to take Norethisterone
4. Possible side effects
5. How to store Norethisterone
6. Contents of the pack and other information
1.What Norethisteroneis and what is it used for
Norethisterone tablets belong to a group of medicines called progestogens. These work by acting on receptors in the body to mimic or exaggerate the effects of the natural hormone, progesterone.
Norethisterone tablets may be used to treat:
- or prevent abnormal or unexpected bleeding from the uterus
- the symptoms of pre-menstrual syndrome which occur before a period including breast pain, headache, migraine, water retention and mood disturbances
- painful or heavy periods
- certain types of breast cancer.
The tablets can also be used to stop periods.
- What do you need to know Before you take Norethisterone
Before you take Norethisterone
Your doctor will discuss your medical and family history with you. Your doctor will also need to check your blood pressure and make sure you are not pregnant. You may also need additional checks, such as a breast examination, that will be specific to your medical needs and/or concerns.
Do not take Norethisterone tablets and tell your doctor if you have:
- if you are allergic to norethisterone or any of the other ingredients of this medicine (listed in section 6).
- pregnant or if you think you might be pregnant
- or if you have:
- ever had a problem with your blood circulation. This includes a blood clot (thrombosis) in the legs (deep vein thrombosis), lungs (pulmonary embolism), heart (heart attack), brain (stroke) or any other parts of the body
- any symptoms of a blood clot, such as chest pain, unexplained and often sudden shortness of breath and/or cough
- any condition which makes you more at risk of a blood clot (thrombosis)
- ever suffered migraine with visual disturbance
- (or are recovering from) a liver disease and the blood tests show that your liver is not yet working normally
- (or have ever had) liver tumours.
- diabetes with damaged blood vessels.
- any type of cancer which might be made worse by exposure to female sex hormones (including breast cancer).
- problems with genital bleeding for which the cause is not yet known.
- a condition called endometrial hyperplasia which has not been treated.
In addition, do not take Norethisterone tablets if you have had any of the following conditions when you were pregnant:
- yellowing of the skin (idiopathic jaundice of pregnancy)
- itching of the whole body (pruritus of pregnancy)
Warnings and precautions
Talk to your doctor or pharmacist before taking Norethisterone tablets if you:
- have diabetes. Norethisterone tablets can produce changes in blood sugar levels. If you are diabetic, your doctor will check your blood sugar before starting treatment and regularly during treatment.
- are overweight (BMI≥30kg/m2)
- have high blood pressure
- have a heart valve disorder or a certain heart rhythm disorder (heart problems)
- have had a thrombosis/embolism or anyone in your close family has had a thrombosis, a heart attack or a stroke at a young age
- suffer from migraine, asthma, or kidney problems
- suffer from epilepsy (see “Other medicines and Norethisterone tablets”)
- have an inflammation of your veins (superficial phlebitis)
- have varicose veins
- have anyone in your immediate family who has had breast cancer
- have previously had a condition called chloasma where the skin on your face may develop brownish blotches. You may be advised to avoid exposure to the sun and to ultraviolet light while you are taking Norethisterone tablets.
- have previously suffered from depression.
- or someone in your close family has ever had high blood levels of cholesterol or triglycerides (fatty substances)
- have a disease of the liver or gall bladder
- have certain rare medical conditions such as systemic lupus erythematosus (SLE), sickle cell disease, Crohn’s disease or ulcerative colitis
- have haemolytic uremic syndrome (‘HUS)’
- have a condition that occurred for the first time or worsened during pregnancy or previous use of sex hormones (e.g. hearing loss, porphyria, or Sydenham’s chorea)
- have hereditary angioedema. Consult your doctor immediately if you experience symptoms of angioedema such as swollen face, tongue or throat, and/or difficulty swallowing, or hives, together with difficulty breathing. Products containing oestrogens may induce or worsen symptoms of angioedema
- have an intolerance to some types of sugar (galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption)
- are using other medications as mentioned in “Other Medicines & Norethisterone tablets”.
Tell your doctor before you take Norethisterone tablets if any of these applies to you. Also tell your doctor if any of these conditions develop or worsen while you are taking Norethisterone tablets, because you may need to stop taking it.
Norethisterone tablets and blood clots:
The main ingredient in Norethisterone (progestogen) is partly converted into oestrogen so you should also consider the general warnings given for combined oral contraceptive pills (“the Pill”).
Do not take Norethisterone tablets if you have a blood clot or have any medical condition which makes you more at risk of developing clots.
The risk of blood clots occurring in the veins and arteries is slightly greater in women who take the combined oral contraceptive pill than in women who don’t. People do not always fully recover from such blood clots, which can cause strokes, heart attacks and bleeding into the brain (subarachnoid haemorrhage). In very rare cases these blood clots can be fatal.
You are more at risk of having a blood clot:
- as you get older
- if you’re off your feet for a long time because of major surgery, injury or illness.
- if you smoke
- if you or any of your close family have had blood clots
- if you are overweight (BMI ≥ 30kg/m2)
- if you have a disorder of blood fat (lipid) metabolism
- if you have a blood disorder
- if you have high blood pressure
- if you suffer from migraines
- if you have a heart valve disorder or a particular type of irregular heartbeat (atrial fibrillation)
- if you have recently had a baby
- if you have diabetes
- if you have certain medical conditions such as systemic lupus erythematosus (SLE), sickle cell disease, Crohn’s disease or ulcerative colitis
Tell your doctor if any of these apply to you. Taking Norethisterone tablets may add to this risk so it may not be suitable for you.
To reduce the risk of blood clots, treatment with Norethisterone tablets must be stopped:
- six weeks before any planned major operation
- before any surgery to the legs
- before medical treatment for varicose veins
- if you are going to be immobilised for a long time (e.g. if you need bed-rest after an accident or operation, or if you have a plaster cast on a broken leg)
Signs of a blood clot include:
- a migraine for the first time or one that is worse than normal
- unusually frequent or severe headaches
- any sudden changes to your eyesight (such as loss of vision or blurred vision)
- any sudden changes to your hearing, speech, sense of smell, taste or touch
- pain or swelling in your leg
- stabbing pain when you breathe
- coughing for no apparent reason
- pain and tightness in the chest
- sudden weakness or numbness in one side or part of your body
- dizziness or fainting.
See a doctor as soon as possible if you notice any possible signs of blood clot. Do not take any more Norethisterone tablets until your doctor says you can.
Norethisterone tablets and cancer
If you have breast cancer, or have had it in the past, you should not take combined oral contraceptives (the Pill). The Pill slightly increases your risk of breast cancer. This risk goes up the longer you’re on it, but returns to normal within about 10 years of stopping it. Because breast cancer is rare in women under the age of 40, the extra cases of breast cancer in current and recent Pill users is small. For example:
- Of 10,000 women who have never taken the Pill, about 16 will have breast cancer by the time they are 35 years old.
- Of 10,000 women who take the Pill for 5 years in their early twenties, about 17–18 will have breast cancer by the time they are 35 years old.
- Of 10,000 women who have never taken the Pill, about 100 will have breast cancer by the time they are 45 years old.
- Of 10,000 women who take the Pill for 5 years in their early thirties, about 110 will have breast cancer by the time they are 45 years old.
Your risk of breast cancer is higher if:
- you have a close relative (mother, sister or grandmother) who has had breast cancer
- you are overweight (BMI ≥ 30kg/m2)
See a doctor as soon as possible if you notice any changes in your breasts, such as dimpling of the skin, changes in the nipple or any lumps you can see or feel.
Very rarely, the Pill has been linked with some forms of liver cancer in women who take it for a long time. These may lead to bleeding in the abdomen.
Taking the Pill has also been linked to liver diseases, such as jaundice and non-cancerous liver tumours, but this is rare.
- See a doctor as soon as possible if you get severe pain in your stomach that does not go away, or yellow skin or eyes (jaundice). You may need to stop taking Norethisterone tablets.
If you go to a different doctor than the one who has prescribed you this medicine, or go to the hospital, let them know that you are taking Norethisterone tablets as they may affect certain tests.
Children and adolescents
Other medicines and Norethisterone tablets
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. Especially:
- other hormonal products (oestrogens or progestogens)
- medicines used to treat epilepsy (e.g. phenobarbital, phenytoin, carbamazepine)
- medicines used to treat infections (e.g. rifampicin, nevirapine, tetracyclines, ampicillin, oxacillin, co-trimoxazole, ritonavir, nelfinavir)
- St John’s Wort (hypericum perforatum) (a herbal remedy)
- ciclosporin (to prevent transplant rejection)
- other medicines which can also cause fluid retention such as anti-inflammatory medicines (e.g. ibuprofen) or vasodilators
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine as you should not take these tablets.
Driving and using machines
Norethisterone tablets may make you feel dizzy, drowsy or affect your vision. Make sure you are not affected before you drive or operate machinery.
Norethisterone tablets and lactose
If you have been told you have an intolerance to some sugars, contact your doctor before taking this medicine, as it contains a type of sugar called lactose.
- How to take Norethisterone
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.
This medicine should be taken for as long as your doctor tells you to. If you finish the course of Norethisterone tablets you will usually have a menstrual bleed 2-3 days after the last tablet. If you do not have a period you must make sure you are not pregnant before taking more.
Day one of the cycle is the first day of your period.
The recommended dose is:
- Abnormal bleeding – 1 tablet three times a day for 10 days. Bleeding usually stops within 1-3 days. A period usually starts 2-4 days after stopping treatment.
- Prevention of abnormal bleeding – 1 tablet twice a day from the 19th – 26th day of the cycle.
- Premenstrual syndrome – 2 to 3 tablets a day from the 19th – 26th day of the cycle. You will normally be treated for several months.
- Stopping a period – 1 tablet three times a day starting three days before the expected beginning of the period. Your period should occur 2-3 days after you have stopped taking the medicine.
- Painful periods – 1 tablet three times a day for 20 days starting on the 5th day of the cycle. You will usually be treated for 3-4 cycles.
- Heavy periods – 1 tablet two to three times a day from the 19th – 26th day of the cycle.
- Endometriosis – 2 tablets a day starting on the 5th day of your cycle. If you continue having small bleeds (“spotting”), the dosage may be increased to 4 to 5 tablets a day. Once bleeding has stopped the dosage may be reduced. You will usually be treated continuously for 4-6 months or longer.
- Breast cancer – 8 tablets a day, the dosage may be increased to 12 tablets a day.
Elderly – Not recommended.
Swallow the tablets with water.
If you take more Norethisterone tablets than you should
If you (or someone else) swallow a lot of tablets at the same time, or you think a child may have swallowed any, contact your nearest hospital casualty department or tell your doctor immediately. Signs of an overdose include feeling or being sick, breast enlargement or vaginal bleeding.
If you forget to take Norethisterone tablets
Do not take a double dose to make up for a forgotten dose. If you forget to take a dose take it as soon as you remember it and then take the next dose at the right time.
If you stop taking Norethisterone tablets
Talk to your doctor before you stop taking the tablets and follow their advice.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
- Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Norethisterone tablets and contact your doctor immediately if you develop the following:
- a rise in blood pressure
- jaundice (yellowing of the skin or whites of the eyes)
- migraine-type headaches
- signs of sever hypersensitivity (anaphylaxis): e.g. swelling of the mouth, tongue, face, throat, difficulty breathing, wheezing, severe skin rash, itch, redness
- if you become pregnant
- unusually bad headache
- sever itching (pruritus)
- other liver problems and signs e.g. abdominal pain, nausea, vomiting, tiredness, dark brown urine
- any sudden changes in eyesight, hearing or speech
- any changes in sense of smell or touch
- Hypersensitivity reactions: severe allergic reaction including skin rash, swelling of the face, lips, tongue or throat, or difficulty breathing or swallowing
Symptoms of blood clot formation or symptoms of inflammation of the veins combined with the formation of blood clots (thromnophlebitis):
- unusual pains in your leg(s)
- unusual swelling of your arms or legs
- sharp pains in your chest or sudden shortness of breath
- crushing pains or feelings of heaviness or tightness in your chest
- coughing for no apparent reason
- one side of your body suddenly becoming very weak or numb
Tell your doctor if you notice any of the following side effects or notice any other effects not listed:
- Genital and urinary: breakthrough bleeding, spotting, absence of bleeding, abnormal bleeding (irregular, increase or decrease), alterations of cervical secretions, cervical erosions, prolonged anovulation (not producing a egg), over production of breast milk, breast pain and tenderness
- Gastrointestinal: feeling or being sick
- Heart: blood clotting disorders (in the lower limbs, lungs or eye), increased blood pressure, inflammation of the veins
- Liver: changes in liver function
- Nervous system: depression, headache, dizziness, tiredness, difficulty in sleeping, nervousness, drowsiness, loss of concentration, vision disorders and intolerance to contact lenses
- Metabolic and nutritional: altered blood levels of cholesterol, changes in insulin and glucose control, diabetic cataract, worsening of diabetes mellitus, sugar in the urine
- Skin: acne, hair growth (especially on the top lip or chin), hair loss, rash which may be itchy, worsening of existing skin conditions
- Other: fluid retention, bloating, weight gain, fever, change in appetite, deepening of the voice, changes in the sex drive
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more information on the safety of this medicine.
- How to store Norethisterone
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton/strip after EXP. The expiry date refers to the last day of that month.
Keep the blister strips in the outer carton in order to protect from light. Do not store above 25degrees.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
- Contents of the pack and other information
What Norethisterone contain
The active substance is Norethisterone. Each tablet contains 5mg of the active ingredient.
The other ingredients are lactose, maize starch, magnesium stearate.
What Norethisterone looks like
and contents of the pack
Norethisterone are white circular uncoated tablets.
Pack sizes are 30 tablets.
Taj Pharmaceuticals Limited
220, Mahagujarat Ind. Estate, Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat, INDIA
Marketing Authorization Holder:
Regal sun co., Ltd.Myanmar