Metrinelle 2 mg Tablets

METRINELLE is a hormone preparation indicated for the long-term treatment of endometriosis (painful symptoms of displaced tissue of the lining of the womb) in adolescents after their first menstrual bleeding from 12 years of age onward and in adults. METRINELLE contains a hormone, the progestogen dienogest. METRINELLE tablets cause the shrinking of the endometrial tissue and reduces associated complaints such as pelvic pain and painful monthly bleedings.

Do not take METRINELLE:

• if you are hypersensitive (allergic) to dienogest or any of the other ingredients of METRINELLE listed in section 6 of this leaflet
• if your blood can form blood clots easily (thrombophilia) or if you suffer from a blood clot(s) (thromboembolic disorder) in your veins. If a blood clot breaks away from the veins where it is formed, it may reach and block arteries of the lungs, causing a so-called ”pulmonary embolism”. This may occur for example in the blood vessels of the legs (deep vein thrombosis) and the lungs (pulmonary embolism)
• if you have inherited genetic mutations: BRCA1 and BRCA 2 genes, as you have a higher risk of developing cancer
• early menstrual periods (before the age of 12 years)
• if you have ever had other non-cancerous breast diseases such as atypical hyperplasia (a precancerous condition that affects cells in the breast) or lobular carcinoma in situ (abnormal cells growing in the lining of the milk glands)
• if you have ever had treatment using radiation therapy to the chest or breast
• if you have ever been exposed to diethylstilbestrol (DES), a synthetic oestrogen medicine.
• if you have or have ever had severe arterial disease, including cardiovascular disease, such as a heart attack, stroke (such as transient ischaemic attack or small reversible stroke) or heart diseases which causes a reduced blood supply to the heart (angina pectoris)
• if you have diabetes mellitus with blood vessel damage
• if you suffer or have ever had any liver disease (and your liver function values have not returned to normal). Symptoms of liver disease may be yellowing of the skin and/or itching of the whole body
• if you have or have ever had a benign or malignant liver tumour
• you have or have had a cancer that may grow under the influence of sex hormones (e.g. of the breast or the genital organs)
• if you have any unexplained vaginal bleeding.

If any of these conditions appear for the first time while taking METRINELLE, stop taking it at once and consult your doctor.

Warnings and precautions

Because METRINELLE is not supposed to be used in pregnancy, you are advised to use a non-hormonal method for contraception (barrier contraception e.g. condom) to prevent an unwanted pregnancy. You must not use sex-hormone containing contraceptives of any form (tablet, patch, intrauterine system) while taking METRINELLE. Do not use the rhythm or temperature methods. These methods can be unreliable because METRINELLE alters the usual changes in temperature and cervical mucus that occur during the menstrual cycle.

Tell your doctor before taking METRINELLE:

• if you have high blood pressure or develop high blood pressure while taking METRINELLE
• if you have ever had a blood clot (venous thromboembolism) or anyone in your immediate family has had a blood clot at a relatively early age
• if you are overweight
• if you have a close relative who has had breast cancer
• if you have a liver disease or had symptoms of liver disease that occurred during a previous pregnancy. These symptoms may include yellowing of the skin or eyes or itching all over your body
• if you have ever suffered from depression
• if you have diabetes or had diabetes temporarily during previous pregnancy
• if you have or have had chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face). If so, avoid too much exposure to the sun or ultraviolet radiation.

If you become pregnant while using METRINELLE, there is a higher likelihood of an extrauterine pregnancy (the embryo develops outside the womb). Tell your doctor before you start taking METRINELLE, if you had an extrauterine pregnancy in the past or have an impaired function of the fallopian tube.

Persistent ovarian follicle (often referred to as “functional ovarian cyst”) may occur during the use of METRINELLE. Most of these follicles are not combined with any symptoms. In cases of abdominal complaints that are different from the symptoms you commonly experience from your endometriosis, inform your doctor. In most cases, the enlarged follicle disappears spontaneously during two to three months of observation.

Uterine bleeding Uterine bleeding, for example in women with a condition where the mucous membrane of the uterus (endometrium) grows into the muscle layer of the uterus, called adenomyosis uteri or benign tumours of the womb sometimes called uterine fibroids (uterine leiomyomata), may become worse with the use of METRINELLE. If bleeding is heavy and continuous over time, this may lead to low red blood cell levels (anaemia), which may be severe in some cases. In the event of anaemia, you should discuss with your doctor if you should stop taking METRINELLE.

METRINELLE and thrombosis The risk of having deep venous thrombosis is temporarily increased as a result of an operation or immobilisation (for example, when you have your leg or legs in plaster or splints). In women who use METRINELLE the risk may be yet higher. Tell your doctor you are using METRINELLE well in advance of any expected hospitalisation or surgery. Your doctor may tell you to stop taking METRINELLE several weeks before surgery or at the time of immobilisation. Your doctor will also tell you when you can start taking METRINELLE again after you are back on your feet.

If you have just given birth, you are at an increased risk of blood clots. You should ask your doctor how soon after delivery you can start taking METRINELLE.

METRINELLE and cancer METRINELLE contains dienogest, which may increase the risk of developing breast cancer in women between 40 – 59 years, during long-term use. Breast cancer has been diagnosed slightly more often in women who use hormones, such as METRINELLE, than in women of the same age who do not use hormones. This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the 10 years after stopping use of the hormones. All women on hormone therapy should receive yearly breast examinations by a doctor and perform monthly self examinations of their breasts (see Do not take METRINELLE).

In rare cases benign liver tumours, and even more rarely, malignant liver tumours have been reported. These tumours may lead to internal bleeding. Contact your doctor immediately if you have severe pain in your abdomen.

Changes in bone mineral density (BMD) The use of METRINELLE may affect the strength of the bone of adolescents (12 to under 18 years). If you have an increased risk of getting osteoporosis (weakening of bones due to loss of bone minerals), your doctor will decide whether to prescribe you METRINELLE or not.

Children and adolescents

METRINELLE should not be given to children under the age of 12 years and before their first menstrual bleeding.

Other medicines and METRINELLE

Always tell your health care provider if you are taking any other medicine. (This includes complementary or traditional medicines.) Some medicines may stop METRINELLE from working properly or increase the levels of METRINELLE in your blood, which can cause unexpected changes in uterine bleeding. Tell your doctor or pharmacist if you are currently taking:

• primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate or felbamate (used to treat epilepsy (fits))
• rifampicin (used to treat tuberculosis (TB))
• griseofulvin, ketoconazole, itraconazole or fluconazole (used to treat fungal infections)
• nevirapine, ritonavir, saquinavir, indinavir or nelfinavir (used to treat human immunodeficiency virus (HIV) infection)
• St John’s Wort (herbal medicine used for the treatment of depressive moods)
• cimetidine (used to treat heartburn)
• verapamil or diltiazem (used to treat high blood pressure and angina (chest pain))
• erythromycin, clarithromycin or roxithromycin (antibiotics used to treat infections)
• nefazodone, fluvoxamine or fluoxetine (used to treat depression.

Do not share medicines prescribed for you with any other person. Always take METRINELLE exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. Tablet-taking from the very first pack has to start on day 1 of the natural cycle (i.e. the first day of your menstrual bleeding). The dosage of METRINELLE is one tablet daily without any break, taken preferably at the same time each day with some liquid as needed. Tablets must be taken throughout 28 days without regard to bleeding. This means that after the first pack has been finished, the next should be started without interruptions. Your doctor will tell you how long your treatment with METRINELLE will last. If you have the impression that the effect of METRINELLE is too strong or too weak, tell your doctor or pharmacist.

If you take more METRINELLE than you should In the event of overdosage, consult your doctor or pharmacist without delay. If neither is available, contact the nearest hospital or poison centre.

If you forget to take METRINELLE The efficacy of METRINELLE may be reduced in the event of missed tablets, vomiting and/or diarrhoea (if occurring within 3 to 4 hours after tablet taking). In the event of missed tablet(s), you should take one tablet only, as soon as you remember, and should then continue the next day to take the tablet at your usual time. A tablet not absorbed due to vomiting or diarrhoea should likewise be replaced by one tablet. Do not take a double dose to make up for forgotten individual doses.

If you stop taking METRINELLE You can stop taking METRINELLE, your original endometriosis symptoms may re-occur.

METRINELLE can have side effects. Not all side effects reported for METRINELLE are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking METRINELLE, please consult your healthcare provider for advice. If any of the following happens, stop taking METRINELLE and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of your hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing;
• rash, hives or itching;
• fainting.

These are all very serious side effects. If you have them, you may have had a serious reaction to METRINELLE. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• changes in the way your heart beats
• difficulty in breathing
• signs of thrombosis (formation of a blood clot within a blood vessel), which may include severe pain in the chest which may reach the left arm; any unusual, severe or prolonged headache or migraine attack; an unusual cough; partial or complete loss of vision, or double vision; slurring or speech disability; sudden changes to your hearing, sense of smell or taste; weakness or numbness in any part of your body and severe pain or swelling in either of your legs
• gastrointestinal inflammation (diarrhoea, bloating, stomach pain).

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Frequent side effects:

• increased weight
• nausea (feeling sick), vomiting (being sick), pain in your stomach area, flatulence, swelling or bloating of your stomach
• back pain
• feeling depressed or nervous, problems sleeping, mood changes
• abnormal physical weakness or lack of energy, irritability
• sexual interest decreased
• acne, hair loss
• breast discomfort, hot flushes, ovarian cyst
• uterine/vaginal bleeding, including spotting.

Less frequent side effects:

• urinary tract infection (strong and frequent urge to urinate, pain and burning sensation when urinating, cloudy, bloody or strong smelling urine, abdominal pain, nausea and vomiting)
• anaemia (fatigue, loss of energy, pale skin, cramps in your legs, difficulty with concentration)
• low blood pressure
• tinnitus (ringing in the ears)
• feeling anxious, depressed, mood swings
• diarrhoea, constipation, stomach discomfort, gingivitis (inflammation of your gums)
• dry eyes
• bone pain, muscle spasms, pain or heaviness in your arms or legs
• increased appetite, decreased weight
• dry skin, excessive sweating, excessive or abnormal hair growth, dandruff, nail problems (such as breaking), skin sensitivity to light, pigmentation
• vaginal fungal infection, vaginal dryness or discharge, pelvic pain, atrophic vulvovaginitis (pain with sex, vaginal itchiness or dryness, urge to urinate or burning with urination), benign breast mass, lumps or hardness
• imbalance in the autonomic nervous system (controls unconscious bodily functions, e.g. perspiration) or disturbed attention.

Side effects with an unknown frequency:

• changes in vaginal bleeding, such as frequent, infrequent, decreased, prolonged or irregular bleeding
• loss of bone density in adolescents (12 – 18 years).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects: If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and Reporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of METRINELLE. You can also send an email directly to the company, [email protected] to ensure safety of the product.

• Store at or below 25 °C.
• Protect from light.
• Keep the blister strip in the outer carton until required for use.
• STORE ALL MEDICINES OUT OF REACH OF CHILDREN.
• Do not use after the expiry date printed on the carton / blister.
• Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains and sewerage systems (e.g. toilets).