1 mg / 2.5 mg, 1 mg / 5 mg, 2 mg / 5 mg tablets
estradiol / medroxyprogesterone
1. What Indivina is and what it is used for
Indovina is a preparation used for hormonal substitution therapy ( hormone replacement therapy, HRT ). It contains two female sex hormones; estrogen and a progestogen. Indovina is used for women whose menstruation has stopped ( menopause ), at least 3 years after their last natural menstruation.
Indovina is used to:
Relieve symptoms during and after menopause
When menstruation ends ( menopause ), the woman’s estrogen drops. It can cause problems such as sweating and hot flashes. Individuals relieve these symptoms after menopause. Individuals should only be used if the problems cause problems in daily life.
Prevent osteoporosis
After menopause, some women suffer from osteoporosis. Discuss all possible options with your doctor. If you have an increased risk of fractures (bone fractures) and other medicines that are not suitable for you, you can use Indivina to prevent osteoporosis after menopause.
2. What you need to know before taking Indivina
Do not use Indivina
Medical background and regular check-ups
The use of HRT involves risks that must be taken into account when deciding to start treatment or continue an ongoing treatment.
Experience is limited for the treatment of women whose menstruation has stopped prematurely (when the ovaries have stopped working or the uterus has been removed). If you belong to that group, the risks of HRT may be different. Talk to your doctor.
Before starting treatment (or resuming treatment), your doctor will ask about your own, and your family’s, medical background. Your doctor may do a general medical and gynecological examination, which also includes the examination of your breasts.
Once you have started treatment, you should go for regular medical check-ups, at least once a year. During these check-ups, you should discuss with your doctor the benefits and risks of continued treatment.
Perform regular examinations of the breasts according to the doctor’s recommendations.
Do not take Indovina
if any of the following apply to you. If you are not sure, talk to your doctor before taking Indivina.
Do not take Indivina:
- If you have or have had breast cancer or there is a suspicion that you may have it
- If you have or have had estrogen-dependent cancer , such as cancer of the uterine lining (endometrium) or if there is a suspicion of such cancer.
- If you have unexpected genital bleeding that has not been investigated by a doctor.
- If you have endometrial hyperplasia (severe thickening of the uterine lining) and are not being treated for it.
- If you have or have had a blood clot in a vein (venous thromboembolism ), in your legs (deep vein thrombosis ) or in your lungs ( pulmonary embolism ).
- If you have a coagulation disorder , a condition with an increased risk of blood clots (lack of protein C, protein S or antithrombin).
- If you have or have had a disease caused by blood clots in the arteries are as heart attack , stroke (stroke) or angina .
- If you have or have had any liver disease and still have abnormal liver values.
- If you have porphyria , a rare inherited blood disorder.
- If you are allergic to estradiol valerate, medroxyprogesterone acetate or any of the other ingredients of this medicine (listed in section 6).
If any of the above affects you the first time you use Indovina, stop taking Indovina and contact your doctor immediately.
Warnings and cautions
Talk to your doctor before starting treatment if you have or have had any of the following problems before starting treatment. They may recur or worsen during treatment with Indivina. Should this occur, have more frequent check-ups with a doctor.
- if you have any disease affecting the lining of the uterus, as well as muscle knots ( fibroids ),
- endometriosis or has had endometrial hyperplasia (severe thickening of the uterine lining).
- if you have an increased risk of getting a blood clot (see below “Blood clots in a vein ( thrombosis )”)
- if a close relative has had breast cancer or other estrogen-dependent cancer.
- high blood pressure
- liver disease eg liver adenoma (benign tumor )
- diabetes
- gallstone disease
- if you get a migraine or severe headache
- if you have systemic lupus erythematosus ( SLE ) – an autoimmune disease that affects many organs in the body
- epilepsy
- asthma
- otosclerosis (ossification of the middle ear leading to hearing loss)
- hypertriglyceridemia (elevated blood lipids)
- fluid retention due to heart or kidney disease
- angioedema (hereditary and acquired).
You should contact a doctor immediately and discontinue treatment if any of the following occur:
- Some of what is mentioned in the section ‘Do not take Indivina’
- If skin or whites of the eyes turn yellow (jaundice); it may be a symptom of liver disease
- If your blood pressure rises sharply (symptoms may include headache, fatigue or dizziness)
- If you are experiencing migraine-like headaches for the first time
- If you become pregnant
- If you get symptoms of a blood clot, such as:
- painful swelling and redness of the legs
- sudden chest pain
- breathing difficultiesFor further information, see below “Blood clots in a vein ( thrombosis )”
Note: Indovina is not a contraceptive. If it is less than 12 months since your last period, or if you are under 50, you may still need to use contraception to avoid pregnancy. Consult your doctor.
HRT and cancer
Severe thickening of the uterine lining ( endometrial hyperplasia ) and cancer of the uterine lining (endometrial cancer)
The use of HRT with estrogen alone increases the risk of severe thickening of the uterine lining and cancer of the uterine lining.
The progestogen in Indovina protects you against this extra risk.
Irregular bleeding
Irregular spotting or spotting may occur during the first 3 to 6 months of taking Indivina.
But about the bleeding,
- lasts longer than 6 months
- begins after taking Indivina for 6 months
- continues after you stop taking Indivina
you should see a doctor as soon as possible.
Breast cancer
Data show that hormone replacement therapy ( HRT ) with a combination of estrogen-progestogen or with estrogen alone, increases the risk of breast cancer. The increased risk depends on how long you use HRT. The increased risk is seen within 3 years. When treatment is stopped, the increased risk decreases over time, but it can persist for 10 years or more if you have used HRT for more than 5 years.
Comparison
Of 1,000 women aged 50–54 who do not take HRT, an average of 13 to 17 will be diagnosed with breast cancer over a 5-year period.
In women who are 50 years old and start taking HRT with estrogen alone for 5 years, 16-17 cases per 1,000 users (ie 0-3 extra cases) will occur.
In women who are 50 years old and start taking HRT with estrogen-progestogen for 5 years, there will be 21 cases per 1,000 users (ie 4-8 extra cases).
Among women aged 50-59 who do not take HRT, an average of 27 out of 1,000 will be diagnosed with breast cancer over a 10-year period.
In women who are 50 years old and start taking HRT with estrogen alone for 10 years, 34 cases per 1,000 users (ie 7 extra cases) will occur.
In women who are 50 years old and start taking HRT with estrogen-progestogen for 10 years, 48 cases per 1,000 users (ie 21 extra cases) will occur.
Check your breasts regularly. Contact a doctor if you notice changes such as:
- indentations or pits
- changes of the nipple
- nodules you can see or feel
It is also recommended that you participate in a mammography examination when you are called to do so. At the mammogram, it is important that you tell the nurse/healthcare professional who performs the examination that you are using HRT, as this medicine may increase the density of the breasts. An increased density in the breasts can make it more difficult to detect lumps on the mammography images.
Ovarian cancer ( ovarian cancer )
Ovarian cancer is rare – much more rare than breast cancer. Use of HRT with estrogen alone or combined estrogen-progestogen has been associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer varies with age. The diagnosis of ovarian cancer will, for example, be made on about 2 women out of 2,000 aged 50 to 54 who do not take HRT for a 5-year period. For women who have taken HRT for 5 years, there will be about 3 cases per 2,000 users (ie about 1 extra case).
How HRT affects the heart and blood circulation
Blood clots in a vein ( thrombosis )
The risk of blood clots in the veins is 1.3‑3 times higher for women who take HRT than for those who do not, especially during the first year of treatment. Blood clots can be serious. If a blood clot ends up in the lungs, it can cause chest pain, shortness of breath, collapse or even lead to death.
You are more likely to get a blood clot in a vein if any of the following apply to you. Tell your doctor if any of the following apply to you:
- You have not been able to walk or stand for a long time due to a major operation, injury or illness (see also section 3, “If you need surgery”).
- You are severely overweight ( BMI over 30 kg / m 2 )
- You have a coagulation disorder that requires long-term treatment with drugs that prevent blood clots
- If a close relative has had a blood clot in the bone, lung or other organ
- You have SLE (systemic lupus erythematosus)
- You have cancer
The symptoms of a blood clot are described in the section “You should contact a doctor immediately and stop the treatment”.
Comparison
For women in their 50s, who do not take HRT, over a 5-year period, an average of 4-7 out of 1,000 users are expected to get a blood clot in a vein.
For women in their 50s who have taken HRT with estrogen-progestogen for more than 5 years, 9-12 out of 1,000 users are expected to get a blood clot in a vein (ie 5 extra cases).
Heart disease (heart attack)
There is no evidence that HRT prevents heart attacks.
For women over the age of 60 who take HRT with estrogen-progestin, the risk of developing heart disease is slightly higher than those who do not take HRT.
Stroke (apoplexy)
The risk of stroke is about 1.5 times higher for those who take HRT compared to those who do not. The risk of stroke is age-dependent, therefore the number of cases of stroke increases due to the use of HRT with increasing age.
Comparison
For women in their 50s who do not take HRT, an average of 8 out of 1,000 people is expected to have a stroke over a 5-year period.
For women in their 50s who have taken HRT for more than 5 years, 11 out of 1,000 users are expected to have a stroke (ie 3 extra cases).
Other conditions
- Using HRT does not prevent memory loss. The risk of memory loss may be slightly higher in women who start using HRT after the age of 65. Consult your doctor.
- If you are taking hormone therapy for thyroid disease (eg thyroxine), your doctor may want to check your thyroid function more often when you are being treated with Indivina.
- If you have or have had chloasma (yellowish-brown pigmentation of the skin, especially in the face), do not expose yourself to sunlight or ultraviolet light when taking Indivina.
Other drugs and Indivina
Some medicines may affect the effect of Indovina, which may lead to irregular bleeding. The following applies:
- Antiepileptic drugs (eg phenobarbital, phenytoin and carbamazepine)
- Medicines for tuberculosis (eg rifampicin, rifabutin)
- Medicines for HIV – infection and hepatitis C virus infections (so-called protease inhibitors and non- nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz, ritonavir and nelfinavir)
- Herbal medicine containing St. John’s wort (Hypericum perforatum)
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription and herbal remedies.
Results from blood test analyze
If you need to take a blood sample, tell your doctor, or the person taking the blood sample, that you are taking Indivina as it may affect the results of some tests.
Pregnancy and breastfeeding
Indovina is intended for women whose menstruation has stopped. If you become pregnant, stop taking Indovina and consult a doctor.
Driving and using machines
Indovina does not affect your ability to drive or use machines.
Indivina contains lactose
This medicine contains 78.9 mg (1 mg / 2.5 mg tablet), 76.5 mg (1 mg / 5 mg tablet) or 75.5 mg (2 mg / 5 mg tablet) of lactose (monohydrate) . If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
3. How to take Indivina
Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.
Your doctor will strive to give you the lowest dose, which will give you symptom relief, and that you should use Indovina for the shortest possible time. Talk to your doctor if you do not get any relief from the symptoms, or feel that the dose is too high.
Take one Indivina tablet daily, preferably at about the same time. Calendar days printed on the blister disc help you keep track of your daily tablet intake. Swallow the tablet whole, with a drink. Normally you start with the lowest dose of Indovina, which is increased if needed. Your doctor will strive to prescribe the lowest possible dose for the shortest possible time which will give you symptom relief. Contact your doctor if you do not get symptom relief after three months. If you have the impression that the effect of Indovina is too strong or too weak, do not change the dose or stop taking the tablets on your own, without consulting your doctor.
If you are not menstruating and if you have not previously used hormone replacement therapy or are switching from another continuous HRT combination medicine, treatment with Indovina can be started at any day.
If you switch from a cyclic HRT treatment, start treatment with Indovina one week after taking the last tablet of cyclic HRT. If you are not sure, talk to your doctor or pharmacist.
While using Indovina
When you start using Indovina, you may experience bleeding at odd times for a few months (see also the section above on endometrial cancer). Tell your doctor if this still happens after a few months or if the bleeding is heavy.
If you take more Indivina than you should
If you have ingested too much medicine or if e.g. If a child has ingested the medicine by mistake, contact a doctor, hospital, or the Poison Information Center for risk assessment and advice. Overdose of Indivina may cause nausea, headache and uterine bleeding.
If you forget to take Indivina
It is best to take the tablet at the same time each day. Do not take a double dose to make up for a forgotten dose . Then continue to take the next tablet at the usual time. Forgetting a tablet or irregular use of Indivina tablets may cause breakthrough bleeding or splashing.
If you stop taking Indivina
If you want to stop taking Indivina, you should first discuss this with your doctor. Your doctor will explain what it means to stop treatment and discuss other options with you.
If you need surgery
If you are going to have surgery, tell your surgeon that you are taking Indivina. You may need to stop taking Indivina for 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, “Blood clots in a vein ( thrombosis )”).
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects , although not everybody gets them. Especially in the beginning (during the first months of treatment) e.g. irregular bleeding occur. Side effects often disappear with continued treatment.
There are several situations in which you may need to stop taking Indivina. Tell your doctor immediately if you:
• Gets symptoms of jaundice (yellow skin and whites of the eyes)
• Having migraine- like headaches for the first time
• If you become pregnant
• If you get noticeably higher blood pressure .
The following diseases are more common in women who take HRT than those who do not:
• Breast cancer
• Severe thickening of the uterine lining ( endometrial hyperplasia ) or cancer of the uterine lining (endometrial cancer)
• Ovarian cancer ( ovarian cancer )
• Blood clot in veins in bones or lungs (venous thromboembolism )
• Heart disease
• Stroke (apoplexy)
• Probable memory loss, if treatment with HRT is started after the age of 65.
See section 2 for more information on these side effects .
The following side effects have been associated with HRT treatment:
Common (may affect up to 1 in 10 people):
- weight gain or loss, swelling caused by fluid retention
- depression, nervousness, lack of energy
- headache, dizziness
- hot flashes, increased sweating
- nausea, vomiting, stomach cramps, gas
- tension and pain in the breasts, discharge, bleeding or breakthrough bleeding, diseases of the external genitalia / vagina, menstrual disorders.
Uncommon (may affect up to 1 in 100 people):
- benign breast tumor, benign growth of the uterine lining
- allergic reaction ( hypersensitivity reaction )
- increased appetite, high levels of cholesterol in the blood
- anxiety, difficulty sleeping, apathy , mood swings , difficulty concentrating, changes in sexual drive and mood, euphoria , agitation
- migraine , feeling of tingling, ant crawling and numbness of the skin, tremors
- visual disturbances, dry eyes
- palpitation
- high blood pressure , superficial inflammation of a vein, purple spots reminiscent of bruises
- shortness of breath, runny or stuffy nose
- constipation, indigestion / heartburn, diarrhea, rectal problems
- acne , hair loss, dry skin, nail changes, skin nodules, severe hair growth ( hirsutism ), painful red skin nodules (erythema nodosum) , itchy rash on the skin
- joint problems, muscle cramps
- increased frequency of urination or increased urination, lack of bladder control, urinary tract infection, discoloration of the urine, blood in the urine
- breast enlargement, breast tenderness, thickened endometrium, diseases of the uterus
- fatigue, abnormal results of laboratory tests, weakness, fever, flu-like symptoms , general malaise.
Rare (may affect up to 1 in 1,000 people):
- hypersensitivity to contact lenses
- changes in liver function and bile flow
- rash
- blood clots, usually in a bone or lung, which cause pain, swelling or redness
- painful menstruation, PMS-like syndrome
Has been reported (occurs in an unknown number of users):
- tumor is in the uterus
- exacerbation of symptoms of angioedema (hereditary and acquired)
- decreased blood flow to the brain or to a part of the brain
- abdominal pain, bloating, yellowing of the skin or eyes
- eczema .
The following side effects have been reported with other HRTs:
- heart disease (heart attack)
- gallbladder disease
- inflammation of the pancreas
- skin diseases:
- yellow-brown pigment spots on the skin, especially on the face (chloasma)
- annular redness or sore rash (erythema multiforme)
- possible memory loss after age 65.
Reporting of side effects ar
If you get any side effects , talk to your doctor or pharmacist. This also applies to any side effects not mentioned in this information. You can also report side effects directly (see details below). By reporting side effects , you can help increase drug safety information.
The Medical Products Agency
Box 26
751 03 Uppsala
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.
5. How to store Indivina
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 or blister. The expiration date is the last day of the specified month.
Do not store above 25 ° C.
Store in the original package. Moisture sensitive.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
The active substances in Indivina tablets are estradiol valerate and medroxyprogesterone acetate.
The tablets are available in three strengths.
Individual 1 mg / 2.5 mg tablets contain 1 mg estradiol valerate and 2.5 mg medroxyprogesterone acetate.
Individual 1 mg / 5 mg tablets contain 1 mg estradiol valerate and 5 mg medroxyprogesterone acetate.
Individual 2 mg / 5 mg tablets contain 2 mg estradiol valerate and 5 mg medroxyprogesterone acetate.
The other ingredients in all Indivina tablets are lactose monohydrate , corn starch, gelatin and magnesium stearate.
What the medicine looks like and contents of the pack
Individual 1 mg / 2.5 mg tablets are white, round, with a bevelled edge, 7 mm in diameter, flat tablets marked 1 + 2.5 on one side.
Individual 1 mg / 5 mg tablets are white, round, bevelled edge, 7 mm in diameter, flat tablets marked 1 + 5 on one side.
Indivina 2 mg / 5 mg tablets are white, round, with a bevelled edge, 7 mm in diameter, flat tablets marked 2 + 5 on one side.
The tablets are packaged in PVC / PVDC aluminum blisters with 28 tablets. Pack sizes of 1 x 28 tablets and 3 x 28 tablets for all three strengths. Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Orion Corporation
Orionvägen 1
FI-02200 Espoo
Finland
Manufacturer
Orion Corporation Orion Pharma
Orionvägen 1
02200 Espoo
Finland
Delpharm Little Sas – Lys Lez Lannoy
Roubaix-Est Activity Park
22 rue de Toufflers
CS 50070
Lys Lez Lannoy 59452
France
For further information on this medicine, please contact your local representative:
Orion Pharma AB, Danderyd
medinfo@orionpharma.com
This medicinal product is authorized under the European Economic Area under the names:
Indivina, Duova