Kliovance® / acetate

Consumer Medicine Information

acetate (MPA). Prevention of loss of What is in this leaflet The researchers stopped the study after density 5 years when it was determined the risks ® After the menopause some women may When you must not use Kliovance 1 were greater than the benefits in this develop fragile (osteoporosis). ® group. The Women’s Health Initiative What Kliovance is used for ...... 1 You should discuss all available options Memory Study indicated increased risk ® with your doctor. Before you take Kliovance ...... 1 of in women aged 65-79 years How to take Kliovance® ...... 4 taking conjugated and MPA. If you are at an increased risk of There are no comparable data currently fractures due to osteoporosis and other While you are taking Kliovance® ... 4 available for other doses of conjugated medicines are not suitable for you, you estrogens and MPA or other ® Side effects ...... 4 can use Kliovance to prevent loss of combinations of estrogens and bone mineral density after menopause. Storage ...... 6 progestagens. Therefore, you should ® assume the risks will be similar for other Kliovance is prescribed for women Product Description ...... 6 medicines containing and who have not had their womb removed, and whose periods stopped more than a Further information ...... 6 progestagen combinations. year ago. User instructions ...... 7 Talk regularly with your doctor about whether you still need treatment with How it works This leaflet answers some common ® questions about Kliovance®, the Kliovance . The menopause, a woman's last menopause (the ‘change of life’), and Treatment with estrogens, with or menstrual period, usually occurs . It does not contain all without progestagens, should be used at between the ages of 45 and 55 years. the available information. It does not the lowest effective dose and for the During this natural life transition, a take the place of talking to your doctor shortest period of time. woman slowly stops producing two or pharmacist. female hormones called estrogen and ® . Menstrual periods All medicines have risks and benefits. What Kliovance is become less frequent until they finally Your doctor has weighed the risks of used for stop. you using Kliovance® against the benefits they expect it will have for you. The falling hormone levels may cause Kliovance® is a type of hormone you to experience uncomfortable Ask your doctor or pharmacist if you replacement therapy (HRT). symptoms such as hot flushes or night have any concerns about using this Kliovance® contains two types of sweats. medicine. female hormone, an estrogen (estradiol) ® The estrogen in Kliovance relieves the and a progestagen (norethisterone Keep this leaflet with the medicine. symptoms caused by a lack of estrogen. acetate). The estradiol in Kliovance® is You may need to read it again. The progestagen protects the lining of identical to the estradiol produced in the your womb from overstimulation by Kliovance® is available only by of women, and is classified as a estrogen. prescription at pharmacies. natural estrogen. is a synthetic progestagen which acts in Your doctor may have prescribed ® When you must not use a similar manner as progesterone, Kliovance for another reason. ® another important female . Ask your doctor if you have any Kliovance ® Kliovance® is used for: questions about why Kliovance has been prescribed for you. Do not use Kliovance® or other Relief of symptoms occurring after estrogens, with or without a menopause progestagen, to prevent heart attacks, Before you take ® stroke or dementia. During the menopause, the amount of Kliovance the estrogen produced by a woman’s A study called the Women’s Health body drops. This can cause symptoms Initiative indicated increased risk of such as hot face, neck and chest (‘hot When you must not take it ® heart attack, stroke, cancer, and flushes’). Kliovance alleviates these Do not take Kliovance® if any of the clots in the legs or lungs in symptoms after menopause. You will following applies to you. Talk to your ® women receiving treatment with a only be prescribed Kliovance if your doctor before taking Kliovance® if product containing symptoms seriously hinder your daily 0.625 mg and the progestagen life. Kliovance® Page 1 of 7 Klvcmi8.docx you are not sure about any of the Talk to your doctor if you have a • asthma points below. premature menopause. • a disease affecting the eardrum and Do not take Kliovance®: The experience in treating women with hearing (otosclerosis) a premature menopause (due to ovarian  if you have, have had or suspect • a very high level of fat in your failure or surgery) is limited. If you blood () having breast cancer have a premature menopause the risks  if you have, have had or suspect of using HRT may be different. • fluid retention due to cardiac or having cancer of the womb lining kidney problems Before you start (or restart) HRT, your (endometrial cancer), or any other • lactose intolerance. estrogen dependent cancer doctor will ask about your own and your family´s medical history. Your doctor Stop taking Kliovance® and see a doctor  if you have any unexplained vaginal may decide to perform a physical immediately bleeding examination. This may include an Stop taking Kliovance® and see a  if you have excessive thickening of examination of your and/or an doctor immediately if you notice any the womb lining (endometrial internal examination, if necessary. of the following when taking HRT: hyperplasia) that is not being ® treated Once you have started on Kliovance • any of the conditions mentioned in you should see your doctor for regular the When you must not take it  if you have or have ever had a check-ups (at least once a year). section. blood clot in a vein (venous thromboembolism), such as in the At these check-ups, discuss with your • yellowing of your skin or the legs (e.g. deep vein thrombosis), or doctor the benefits and risks of whites of your eyes (jaundice). ® the lungs (pulmonary embolism) continuing with Kliovance . These may be signs of a liver  if you have a blood clotting Go for regular breast screening as disease. disorder (such as protein C, protein recommended by your doctor. • a large rise in your blood pressure S or antithrombin deficiency) The experience of treating women older (symptoms may be headache,  if you have or previously have had than 65 years’ is limited. tiredness, dizziness) a disease caused by blood clots in Warnings and precautions • migraine-like headaches which the arteries, such as a heart attack, happen for the first time stroke or angina Tell your doctor if you have ever had any of the following problems, before • if you become pregnant  if you have or have ever had a liver disease and your blood test results you start the treatment, as these may • if you notice signs of a blood clot, have not returned to normal return or become worse during such as: treatment with Kliovance®.  if you have a rare blood problem – painful swelling and redness of called ‘porphyria’ which is passed If so, you should see your doctor more the legs down in families (inherited) often for check-ups: – sudden chest pain  if you are allergic (hypersensitive) • fibroids inside your womb – difficulty in breathing to estradiol, norethisterone acetate • growth of the womb lining outside For more information, see Blood clots in or any of the other ingredients of your womb (endometriosis) or a ® a vein (venous thromboembolism). Kliovance (listed in the history of excessive growth of the ® Ingredients section of this leaflet) womb lining (endometrial Note: Kliovance is not a contraceptive.  if you are pregnant or suspect you hyperplasia) If it is less than 12 months since your may be pregnant, or you are breast- • increased risk of developing blood last menstrual period or you are under 50 years’ old, you may still need to use feeding clots (see Blood clots in a vein additional contraception to prevent  if you have kidney disease (venous thromboembolism)) pregnancy. Speak to your doctor for  if it is after the expiry date • increased risk of getting a advice. (‘Expiry’) printed on the pack estrogen-sensitive cancer (such as  if the packaging is torn or shows having a mother, sister or HRT and cancer signs of tampering grandmother who has had breast Excessive thickening of the lining of the Stop taking Kliovance® at once and cancer) womb (endometrial hyperplasia) and consult your doctor immediately if • high blood pressure cancer of the lining of the womb (endometrial cancer) any of the above conditions appear • a liver disorder, such as a benign for the first time while taking this liver tumour Taking estrogen-only HRT will increase medicine. • diabetes the risk of excessive thickening of the Before you start to take it lining of the womb (endometrial • gallstones hyperplasia) and cancer of the womb Medical history and regular check-ups • migraine or severe headaches lining (endometrial cancer). The use of HRT carries risks which • a disease of the The progestagen in Kliovance® reduces need to be considered when deciding that affects many organs of the this extra risk. whether to start taking it, or whether to body (systemic carry on taking it. erythematosus, SLE) • epilepsy

Kliovance® Page 2 of 7 Klvcmi8.docx Compare use HRT, as this may Looking at women in their 50s who are In women who still have a womb and increase the density of your breasts not taking HRT, on average, over a 5- who are not taking HRT, on average, 5 which may affect the outcome of the year period, 4 to 7 in 1,000 would be in 1,000 will be diagnosed with mammogram. Where the density of the expected to get a blood clot in a vein. endometrial cancer between the ages of breast is increased, mammography may For women in their 50s who have been 50 and 65. not detect all lumps. taking estrogen-progestagen HRT for For women aged 50 to 65 who still have Ovarian cancer over 5 years, there will be 9 to 12 cases in 1,000 users (i.e. an extra 5 cases). a womb and who take estrogen-only Ovarian cancer is rare – much rarer than HRT, between 10 and 60 women in breast cancer. The use of estrogen-only Heart disease (heart attack) 1,000 will be diagnosed with or combined estrogen-progestagen HRT There is no evidence that HRT will endometrial cancer (i.e. between 5 and has been associated with a slightly prevent a heart attack. Women over the 55 extra cases), depending on the dose increased risk of ovarian cancer. The age of 60 years who use estrogen- and for how long it is taken. risk of ovarian cancer varies with age. progestagen HRT are slightly more Irregular bleeding For example, in women aged 50 to 54 likely to develop heart disease than who are not taking HRT, about 2 You may have irregular bleeding or those not taking any HRT. women in 2,000 will be diagnosed with drops of blood (spotting) during the first Stroke ovarian cancer over a 5-year period. For 3-6 months of taking Kliovance®. women who have been taking HRT for The risk of getting stroke is about 1.5 However, see your doctor as soon as 5 years, there will be about 3 cases per times higher in HRT users than in non- possible if the irregular bleeding: 2,000 users (i.e. about 1 extra case). users. The number of extra cases of • carries on for more than the first 6 stroke due to use of HRT will increase Effect of HRT on heart and circulation months with age. Blood clots in a vein (venous • starts after you have been taking Compare ® thromboembolism) Kliovance for more than Looking at women in their 50s who are The risk of blood clots in the veins is 6 months not taking HRT, on average, 8 in 1,000 about 1.3 to 3 times higher in HRT users • carries on after you have stopped would be expected to have a stroke over than in non-users, especially during the taking Kliovance®. a 5-year period. first year of taking it. Breast cancer For women in their 50s who are taking Blood clots can be serious, and if one HRT, there will be 11 cases in Evidence suggests that taking combined travels to the lungs, it can cause chest 1,000 users over 5 years (i.e. an extra 3 estrogen-progestagen and possibly also pain, breathlessness, fainting or even cases). estrogen-only HRT increases the risk of death. breast cancer. The extra risk depends on Other conditions You are more likely to get a blood clot how long you take HRT. The additional in your veins as you get older and if any HRT will not prevent memory loss. risk becomes clear within a few years. of the following applies to you. Inform There is some evidence of a higher risk However, it returns to normal within a your doctor if any of these situations of memory loss in women who start few years (at most 5) after stopping applies to you: using HRT after the age of 65. Speak to treatment. your doctor for advice. • you are unable to walk for a long Compare time because of major surgery, Tell your doctor or the laboratory Women aged 50 to 79 who are not injury or illness ( see also If you staff that you are taking Kliovance® if taking HRT, on average, 9 to 17 in need to have surgery, below) you need a blood test. 1,000 will be diagnosed with breast This is because this medicine can affect • you are seriously overweight (BMI cancer over a 5-year period. the results of some tests. >30 kg/m²) For women aged 50 to 79 who are • you have any blood clotting Taking other medicines taking estrogen-progestagen HRT over problem that needs long-term 5 years, there will be 13 to 23 cases in Tell your doctor if you are taking or treatment with a medicine used to 1,000 users (i.e. an extra 4 to 6 cases). plan to take other medicines, including: prevent blood clots Regularly check your breasts. See  other estrogen medicines • if any of your close relatives has your doctor if you notice any changes ever had a blood clot in the leg,  medicines to help you sleep, such as: lung or another organ including barbiturates • dimpling of the skin  medicines for epilepsy e.g. • you have systemic lupus , carbamazepine, • changes in the nipple erythematosus (SLE) lamotrigine • any lumps you can see or feel. • you have cancer.  some and other anti- Additionally, you are advised to join For signs of a blood clot, see Stop taking infective medicines e.g. rifampicin, mammography screening programs Kliovance® and see a doctor rifabutin, nevirapine, , when offered to you. For mammogram immediately, above. cyclosporin, ritonavir, telaprevir, screening, it is important that you nelfinavir, Compare inform the nurse/healthcare professional  St. John’s Wort – used to treat who is actually taking the x-ray that you depression Kliovance® Page 3 of 7 Klvcmi8.docx  antihistamines – used to treat If you forget to take it Do not take Kliovance® if you are allergies You can always see if you have taken breast-feeding.  and your tablet by looking at the day on the – used to manage blood clotting At your routine check-up, your doctor calendar pack. processes may reassess your continued need for Kliovance®. Your doctor may consider  antidiabetic – used to treat If you forget to take a tablet at the alternative HRT treatments if diabetes usual time, take it as soon as you remember. If it is almost time for troublesome symptoms remain.  medicines which decrease serum folate your next dose, throw away the tablet If you have any concerns about taking you missed and take your next dose Kliovance®, ask your doctor or  – used to treat when you are meant to. pharmacist. If your doctor tells you to malfunction of the thyroid gland ® You may have vaginal bleeding or stop taking Kliovance , return any  – used to treat unused medicine to your pharmacist. inflammatory conditions spotting if you forget to take your tablets. Or other specific medicines including: Things you must not do  imipramine If you take too much This medicine is for you only. Do not  pethidine (overdose) give it to someone else even if they Tell your doctor if you are taking any If you take more tablets than you seem to have the same symptoms as other medicines, including any that have been prescribed, contact your you. you buy without a prescription from doctor for advice. Do not take Kliovance® to treat any your pharmacy, supermarket or Overdose may cause nausea and other complaints unless your doctor health food shop. vomiting. tells you to. The effect of Kliovance® can be reduced Do not change the way you take by other medicines, and may affect your If you need to have surgery Kliovance®, or lower the dosage, vaginal bleeding pattern. Tell the surgeon that you are taking without checking with your doctor. Kliovance® if you are going to have How to take Kliovance® surgery. You may need to stop taking Side effects Kliovance® about 4 to 6 weeks before How to take it the operation to reduce the risk of a All medicines can have side effects. For further information on the use of the blood clot (see Blood clots in a vein Sometimes they are serious, most of the calendar pack, see User Instructions at (venous thromboembolism)). time they are not. the end of the package leaflet.Your Ask your doctor when you can start Tell your doctor or pharmacist if you doctor will tell you when to start taking taking Kliovance® again. ® experience any side effects while you the tablets. Kliovance treatment are taking Kliovance® (whether or not should usually start a year after your they are mentioned below). periods stop. While you are taking Kliovance® You may need medical treatment if you If you are not already using HRT, you experience some of the side effects. can start Kliovance® at a convenient You can expect your symptoms to ® time for you. If you are already using a When you start taking Kliovance your improve within a few weeks of starting body has to adjust to new hormone different type of HRT, your doctor can ® Kliovance . However, you will not be levels. You may experience the advise you when to switch to ® ® aware of the effect of Kliovance on Kliovance . following side effects: your bones. Take one tablet once a day, at about the  breast tenderness, pain or Kliovance® can be stopped at any time. same time each day. enlargement You should discuss this with your  irregular periods or excessive Once you have finished all the 28 doctor. bleeding during your periods tablets in the pack, start a new pack You should include foods that are good  period pain continuing the treatment without sources of and D in  abdominal (stomach) pain, interruption. your daily diet, and exercise regularly. indigestion, feeling sick (nausea), How long to take it Calcium, and exercise help vomiting, diarrhoea, bloating, prevent thinning of the bones. Your flatulence HRT should be prescribed at the lowest doctor can advise you on which foods  skin rash or itching, skin reactions, effective dose and for the shortest and type of exercise are best for you. duration necessary (see Before you start acne, changes in hair growth, hair to take it). Your doctor can advise you Stop taking Kliovance® and contact loss how long you may need to take your doctor if you become pregnant.  inflammation of a vein Kliovance®. Kliovance® is for use in postmenopausal  changes in sexual appetite, women only. problems getting to sleep, The continuation of the treatment should nervousness, anxiety be re-evaluated annually.  headache, migraine, dizziness Kliovance® Page 4 of 7 Klvcmi8.docx  fungal of the vagina This list includes very serious side These blood clots are not always (thrush), vaginal inflammation or effects. You may need urgent medical serious, but if one travels to the lungs, it itching attention or hospitalisation. These side can cause chest pain, breathlessness, collapse or even death. This condition is  gallbladder problems, gallstones effects are very rare.  leg cramps called pulmonary embolism, or PE. Effects on your heart or DVT and PE are examples of a  back pain circulation condition called venous  weight change thromboembolism, or VTE.  swelling due to fluid retention Heart disease You are more likely to get a blood clot (oedema) Talk to your doctor to see if you if:  visual disturbances should be taking HRT if you have  you are seriously overweight  aggravation, occurrence or ever had heart disease.  you have had a blood clot before recurrence of uterine fibroids HRT is not recommended for women  any of your close family have had (benign tumours) who have heart disease, or have had blood clots ®  Kliovance does not treat your heart disease recently.  you have had one or more symptoms effectively. HRT will not help to prevent heart miscarriages These side effects are usually temporary disease.  you have any blood clotting and disappear. Studies with one type of HRT problem that needs treatment with a Tell your doctor if: (containing conjugated estrogen plus the medicine such as warfarin progestagen MPA) have shown that  you’re off your feet for a long time  you think you may be suffering from depression women may be slightly more likely to because of major surgery, injury or get heart disease during the first year of illness  you are not feeling well or find any taking the medication. For other types of side effect too uncomfortable or  you have a rare condition called HRT, the risk is likely to be similar, unacceptable systemic lupus erythematosus (SLE although this is not yet certain. – an autoimmune disease).  any side effect becomes worse See a doctor as soon as possible and If any of these things apply to you,  vaginal bleeding or spotting do not take any more HRT until your talk to your doctor to see if you suddenly becomes heavier. doctor says you can if you get: should take HRT. Tell your doctor immediately if any of  a pain in your chest that spreads to the following conditions occur See a doctor as soon as possible and your arm or neck. (because you may be told to stop do not take any more HRT until your taking Kliovance®): This pain could be a sign of heart doctor says you can if you get: disease.  painful swelling in your leg  severe pain or swelling in your legs Stroke  sudden chest pain  yellow colouring of the skin and Recent research suggests that HRT eyes (jaundice)  difficulty breathing. slightly increases the risk of having a These may be signs of a blood clot.  migraine or sudden severe stroke. Other things that can increase the headache, and you have not risk of stroke include: Effects on your risk of previously had migraines  getting older developing cancer  problems with your eyesight which  high blood pressure develop suddenly Breast cancer  smoking  marked rise in blood pressure Women who have breast cancer, or have  drinking too much alcohol had breast cancer in the past, should not  you can see or feel a lump in your  an irregular heartbeat. breast, or you notice dimpling of take HRT. the skin or changes in the nipple Talk to your doctor to see if you Taking HRT slightly increases the risk should take HRT if you are worried  you know or suspect you are of breast cancer; so does having a later about any of these things, or if you pregnant. menopause. The risk for a post- have had a stroke in the past. menopausal woman taking estrogen- Tell your doctor immediately or go to only HRT for 5 years is about the same Accident and Emergency at your See a doctor as soon as possible and do not take any more HRT until your as for a woman of the same age who’s nearest hospital if you notice any of doctor says you can if you get: still having periods over that time and the following: not taking HRT. The risk for a woman  unexplained migraine-type who is taking estrogen plus progestagen  skin rashes over a large part of the headaches, with or without HRT is higher than for estrogen-only body disturbed vision. These headaches HRT (but estrogen plus progestagen  shortness of breath, wheezing may be an early warning sign of a HRT is beneficial for the endometrium, stroke.  swelling of the face, lips or tongue see Endometrial cancer below). Blood clots  fast pulse HRT may increase the risk of blood For all kinds of HRT, the extra risk of  sweating clots in the veins (also called deep vein breast cancer goes up the longer you thrombosis, or DVT), especially during take it, but returns to normal within the first year of taking it. about 5 years after stopping HRT. Kliovance® Page 5 of 7 Klvcmi8.docx Your risk of breast cancer is also higher ovarian cancer in some epidemiological Manufacturer if: studies. Kliovance® is made in Denmark and  you have a close relative (mother, In addition to the possible side effects supplied in Australia by: sister or grandmother) who has had listed above, dementia has been breast cancer reported with HRT. Novo Nordisk Pharmaceuticals Pty. Ltd.  you are seriously overweight. Level 3 Do not be alarmed by this list of 21 Solent Circuit Make an appointment to see your possible side effects. doctor as soon as possible if you You may not experience any of them. Baulkham Hills NSW 2153 notice any changes in your breast, This leaflet was prepared on 25 October such as: Ask your doctor or pharmacist to answer any questions you may have. 2016.  dimpling of the skin Australian Registration Number:  changes in the nipple AUST R 67440  any lumps you can see or feel. Storage Kliovance® is a registered trademark of Endometrial cancer (cancer of the lining Keep all medicines out of the sight Novo Nordisk Health Care AG. of the womb) and reach of children. ® Taking estrogen-only HRT for a long NovoCare is a registered trademark of Do not use this medicine after the Novo Nordisk A/S. time can increase the risk of cancer of expiry date which is stated on the the lining of the womb (the carton and label. © 2016 endometrium). Taking a progestagen as The expiry date refers to the last day of Novo Nordisk A/S well as the estrogen helps to lower the that month. extra risk. Keep Kliovance® in a cool dry place Further information If you still have your womb, your doctor where the temperature stays below may prescribe a progestagen as well as 25oC. Do not put Kliovance® in the For further information call the estrogen. If so, these may be prescribed ® refrigerator. NovoCare Customer Care Centre on separately, or as a combined HRT 1800 668 626. product. Keep the calendar pack in the outer carton in order to protect from light. If you have had your womb removed (a www.novonordisk.com.au hysterectomy), your doctor will discuss Do not throw away any medicines with you whether you can safely take down the sink or in your household estrogen without a progestagen. rubbish. Ask you pharmacist how to throw away medicines you no longer If you have had your womb removed use. because of endometriosis, any endometrium left in your body may be These measures will help to preserve the at risk. So your doctor may prescribe environment. HRT that includes a progestagen as well as an estrogen. Product Description Your product, Kliovance®, contains a progestagen. What Kliovance® looks like If you get breakthrough bleeding or Kliovance® comes in a calendar pack. spotting, it’s usually nothing to worry Each pack holds 28 tablets. Each about, especially during the first few Kliovance® tablet is white and round months of taking HRT. and marked ‘NOVO 288’ on one side. Make an appointment to see your The Novo Nordisk logo (Apis bull) is on doctor if the bleeding or spotting: the other side.  carries on for more than the first Ingredients few months Each tablet contains 1mg estradiol (as  starts after you’ve been on HRT for hemihydrate) and 0.5mg norethisterone a while acetate as the active ingredients.  carries on even after you’ve stopped Estradiol is identical to natural human taking HRT. estrogen. Norethisterone acetate is a It could be a sign that your endometrium hormone similar to progesterone. has become thicker. The tablets also contain lactose, maize Ovarian cancer starch, copovidone, talc, Long-term (at least 5 or 10 years’) use stearate, hypromellose and triacetin. of estrogen-only HRTs and estrogen ® plus progestagen HRTs has been Kliovance is gluten-free. associated with an increased risk of

Kliovance® Page 6 of 7 Klvcmi8.docx Kliovance® Estradiol/Norethisterone acetate

User instructions 3. Move the dial every day How to use the calendar On the next day simply move the transparent dial clockwise one space pack as indicated by the arrow. Tip out the next tablet. Remember to take only one tablet once a day. 1. Set the day reminder You can only turn the Turn the inner disc to set the day of transparent dial after the tablet in the week opposite the little plastic the opening has been removed. tab.

2. Take the first day’s tablet Break the plastic tab and tip out the first tablet.

Kliovance® Page 7 of 7 Klvcmi8.docx