tablets
estradiol valerate/medroxyprogesterone acetate
What Trivina is and what it is used for
Trivina is a preparation used for hormone replacement therapy ( HRT ). It contains two female sex hormones; estrogen and progestin. Trivina is used in women whose menstruation has stopped ( menopause ), at least 6 months after their last natural period.
Trivina is used to:
Relieve symptoms during and after menopause
When menstruation stops ( menopause ), the woman’s estrogen drops. It can cause problems such as sweating and hot flashes. Trivina relieves these symptoms after menopause. Trivina should only be used if the symptoms 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 (broken bones) and other medicines are not suitable for you, you can use Trivina to prevent osteoporosis after menopause.
What you need to know before you take Trivina
Medical background and regular check-ups
The use of HRT entails 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 surgically 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. The doctor may perform a general medical and gynecological examination, which also includes an examination of the breasts. Once you have started treatment, you must go for regular medical check-ups, at least once a year. During these checks, you must discuss with the doctor the benefits and risks of continued treatment.
Do regular breast examinations as recommended by your doctor.
Do not take Trivina:
Do not take Trivina if any of the following apply to you. Talk to your doctor before taking Trivina if you are not sure:
- 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 lining of the womb (endometrium), or if such cancer is suspected.
- If you have unexpected abdominal bleeding that has not been investigated by a doctor.
- If you have endometrial hyperplasia (severe thickening of the lining of the uterus) and are not being treated for it.
- If you have or have had blood clots in a vein (venous thromboembolism ), in the legs (deep vein thrombosis ), or the 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 recently had a disease caused by blood clots in the arteries, such as a heart attack, stroke, or angina pectoris.
- 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 or 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 Trivina, stop taking Trivina and contact your doctor immediately.
Warnings and precautions
Talk to your doctor if you have or have had any of the following problems before starting treatment. They may recur or worsen during treatment with Trivina. Should this occur, you should have more frequent check-ups with a doctor.
- If you have any disease affecting the endometrium, as well as muscle knots ( myoma ), endometriosis, or have had endometrial hyperplasia (severe thickening of the endometrium)
- If you have an increased risk of blood clots (see below “Blood clots in a vein ( thrombosis )”)
- If a close relative has had breast cancer or another estrogen-dependent cancer
- High blood pressure
- Liver disease, e.g. 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 attacks many organs in the body
- Epilepsy
- Asthma
- Otosclerosis (ossification of the middle ear leading to hearing loss
- Hypertriglyceridemia (elevated level of blood fats)
- Fluid retention due to heart or kidney disease
- Hereditary and acquired angioedema.
You should immediately contact a doctor and stop the treatment if any of the following occurs :
- Any of the things mentioned in the section ‘Do not take Trivia
- If the skin or whites of the eyes turn yellow (jaundice); it could be symptoms of liver disease
- If you develop symptoms suggestive of angioedema, such as swelling of the face, tongue, and/or throat and/or difficulty swallowing or hives along with difficulty breathing
- If your blood pressure rises sharply (symptoms may include headache, tiredness, or dizziness)
- If you get a migraine-like headache 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 difficulties further information, see below “Blood clots in a vein ( thrombosis )”
Please note: Trivina is not a contraceptive. If it has been 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
Strong thickening of the lining of the uterus ( endometrial hyperplasia ) and cancer of the lining of the uterus (endometrial cancer)
The use of estrogen-only HRT increases the risk of severe thickening of the endometrium and cancer of the endometrium. The progestin in Trivina protects you against this extra risk.
Unexpected bleeding
You will have a bleed every three months (so-called withdrawal bleed) when you take Trivina. But if you have unexpected bleeding or spotting in addition to your period, and these:
– lasts longer than 6 months
– starts after you have taken Trivina for 6 months
– continues after you stop taking Trivina
you should see a doctor as soon as possible.
Breast cancer
Data indicate that treatment with combined estrogen – progestagen, and possibly also with estrogen alone, increases the risk of breast cancer. The risk depends on the treatment time. The extra risk depends on how long you take HRT. The increased risk is seen within a few years but returns to normal within a few years (maximum 5 years) after treatment stops.
Comparison
For women aged 50-79 who do not take HRT, an average of 9-17 out of 1,000 will be diagnosed with breast cancer over 5 years. For women aged 50-79 taking estrogen-progestogen HRT for 5 years, 13-23 out of 1,000 users will be diagnosed (ie 4-6 extra cases).
Check your breasts regularly. Contact a doctor if you notice changes such as :
– indentations or pits
– nipple changes
– nodules you can see or feel
It is also recommended that you participate in mammography screening when you are called to do so. During the mammogram, you must tell the nurse/healthcare staff doing the examination that you are using HRT, as this medicine can increase the density of the breasts. An increase in the density of the breasts can make it more difficult to detect lumps on mammogram images.
Ovarian cancer ( ovarian cancer )
Ovarian cancer is rare – much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestogen HRT has been associated with a slightly increased risk of ovarian cancer. The risk of ovarian cancer varies with age. For example, the diagnosis of ovarian cancer will be given to around 2 women out of 2,000 aged 50 to 54 who do not take HRT for 5 years. For women who have been taking 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 vein a 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 an extended period 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 a leg, lung, or another organ
– You have SLE (systemic lupus erythematosus)
– You have cancer
The symptoms of blood clots are described in the section “You should immediately contact a doctor and stop the treatment”.
Comparison
For women in their 50s who do not take HRT, over 5 years an average of 47 out of 1,000 are expected to have a blood clot in a vein. For women in their 50s who have been taking estrogen-progestin HRT for more than 5 years, 9-12 out of 1,000 users are expected to develop 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 60 who take HRT with estrogen-progestogen, the risk of developing heart disease is slightly higher than for those who do not take HRT.
Stroke _
The risk of stroke is approximately 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 due to the use of HRT increases with increasing age.
Comparison
For women in their 50s, who do not take HRT, over 5 years, an average of 8 out of 1,000 are expected to have a stroke.
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
- HRT use 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.
- Estrogen treatment can cause fluid to accumulate in the body ( edema ), especially in women who suffer from impaired heart or kidney function.
- The results of some laboratory tests (eg tests that measure thyroid function and liver function) may be affected by Trivina treatment.
- Estrogen treatment can cause an increase in blood fat values ( triglycerides ), which in women with elevated levels of blood fats can lead to the risk of inflammation of the pancreas ( pancreatitis ).
- Women prone to skin discoloration (chloasma) should minimize exposure to sunlight or ultraviolet light during treatment with Trivina.
Other medicines and Trivina
Some medicines can affect the effect of Trivina, which can lead to irregular bleeding. This applies to the following:
- Medicines for epilepsy (eg phenobarbital, phenytoin, and carbamazepine)
- Medicines for tuberculosis (e.g. rifampicin, rifabutin)
- Medicines for HIV infection (eg nevirapine, efavirenz, ritonavir and nelfinavir)
- Natural remedies containing St. John’s wort (Hypericum perforatum)
- Medicines against hepatitis C virus ( HCV ) (e.g. combination treatment ombitasvir/paritaprevir/ritonavir with or without dasabuvir as well as treatment with glecaprevir/pibrentasvir) can cause increased liver values which can be seen in blood tests (increase in ALT liver enzyme) in women using combined hormonal contraceptives containing ethinylestradiol. Trivina contains estradiol instead of ethinylestradiol. It is not known whether an increase in ALT liver enzyme may occur when Trivina is used concurrently with this combination of anti- HCV therapy. Your doctor will advise you.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Results from blood test analyses
If you need to have a blood test, you must tell the doctor, or whoever is taking the blood test, that you are taking Trivina as it may affect the results of some tests.
Pregnancy and breastfeeding
Trivina is intended for women whose menstruation has stopped. If you should become pregnant, stop taking Trivina and consult a doctor.
Driving ability and use of machinery
Trivina is not expected to affect the ability to drive or use machines.
Trivina contains lactose
This medicine contains 82 mg (white tablet), 143 mg (blue tablet), and 82 mg (yellow tablet) of lactose (in the form of monohydrate). If you have an intolerance to certain sugars, you should consult your doctor before taking this medicine.
How to take Trivina
Always take this medicine as directed by your doctor or pharmacist. Ask your doctor or pharmacist if you are unsure.
Dosage
Each pack contains three blister cards numbered 1‑3. One tablet is taken daily without a break, preferably at the same time every day. First, take the white, then the blue, and finally the yellow tablets. Then continue without a break on the next Trivina pack. On blister card number 3 there are mini bubbles to mark the first day of treatment. If you choose to start on a Monday, a hole is dotted over Monday. You will have a bleed every 3 months (so-called withdrawal bleed) while taking Trivina.
If you change from a hormone treatment that causes bleeding once a month, you must start the treatment with Trivina the day after you stop the previous medicine.
The doctor aims for you to take the lowest dose that gives you symptom relief and for you to use Trivina for the shortest possible time. Talk to your doctor if you do not get any relief from your symptoms, or feel that dose one would be too high.
Bleeding pattern
During the first months of treatment, breakthroughs or small bleeding may occur. If bleeding persists, contact the doctor for a re-evaluation of the treatment. Continuous or prolonged bleeding during a hormone treatment may in rare cases indicate endometrial hyperplasia or that the dosage is not right for you. If breakthrough or light bleeding only occurs later in the treatment or if it persists after the end of the treatment, contact the doctor.
If you need surgery
If you are going to have surgery, you must inform the operating doctor that you are taking Trivina. You may need to stop taking Trivina for 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, “Blood clots in a vein ( thrombosis )”). Ask the doctor when it is appropriate to start taking Trivina again.
If you have taken too much Trivina
If you have ingested too much medicine or if, for example, a child has ingested the medicine by mistake, contact a doctor or pharmacist for an assessment of the risk and advice.
If you forget to take Trivina
If you forget to take a tablet at the regular time, skip the tablet and take the next tablet at the next regular time. Do not take a double dose to make up for a missed dose.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. The following diseases are more common in women who take HRT than those who do not:
- Breast cancer
- Severe thickening of the lining of the uterus ( endometrial hyperplasia ) or cancer of the lining of the uterus (endometrial cancer)
- Ovarian cancer ( ovarian cancer )
- Blood clots in veins in legs or lungs (venous thromboembolism )
- Heart disease
- Stroke _
- Probable memory loss, if treatment with HRT is started after the age of 65
See section 2 for more information about these side effects.
Other side effects are
The most common side effects usually decrease with continued treatment. With Trivina treatment, breakthrough bleeding and painful withdrawal bleeding are more frequent in the first 2 years after menopause.
Other common side effects are ( may affect up to 1 in 10 users ): Chest tightness/pain. Headache, dizziness. Nervousness, low mood, lethargy. Hot flashes. Abdominal cramps, nausea, vomiting, flatulence. Irregular bleeding from the abdomen, breakthrough bleeding, spotting, discharge, and diseases of the abdomen. Weight gain, weight loss, fluid accumulation (edema). Increased tendency to sweat.
Uncommon side effects ( may affect up to 1 in 100 users ):
High blood pressure, superficial inflammation in the leg blood vessels, minor bleeding in the skin and mucous membranes. Migraine, loss of sensation, tremors. Visual impairment, dry eyes. Palpitation. Benign cancer of the breast or uterus. Allergic reaction. Increased appetite, and increased levels of cholesterol in the blood. Anxiety, insomnia, apathy, emotional instability, difficulty concentrating, change in sexual desire, mood swings, euphoria, agitation. Shortness of breath ( dyspnoea ), runny nose. Constipation, digestive problems ( dyspepsia ), diarrhea, and diseases of the rectum. Acne, hair loss, dry skin, skin nodules, increased hair growth, hives (raised, itchy rash), painful red-purple bumps on the skin (erythema nodosum), hives. Joint diseases, muscle cramps. Urinary urges, increased need to urinate, urinary incontinence, urinary tract infection, discoloration of urine, and blood in the urine. Tender and swollen breasts, abnormal growth of the lining of the uterus ( endometrial hyperplasia ), and diseases of the uterus. Fatigue, abnormal laboratory values, weakness, fever, flu-like symptoms, and malaise.
Rare side effects ( may affect up to 1 in 1,000 users ): Hypersensitivity to contact lenses. Blood clots in the legs or lungs (venous thromboembolism ). Altered liver function and bile flow. Rash. Painful periods, premenstrual syndrome.
Side effects that have been reported (occurring in an unknown number of users): Enlargement of tissue nodules in the uterus (Uterine fibroids). Worsening of symptoms of angioedema (hereditary and acquired as a severe allergic reaction with swelling of the tongue, throat, and eyes). Lack of oxygen in the brain. Stomach pain, flatulence (air in the stomach). The liver disease leads to yellowing of the skin. Eczema.
The following side effects have been reported for other HRT:
- Gallbladder disease
- Myocardial infarction
- Various skin diseases:
- dark skin spots, especially on the face and neck, so-called “pregnancy spots” (chloasma)
- ring-shaped reddened or ulcerated rash (erythema multiforme)
- Inflammation of the pancreas ( pancreatitis )
- Possible dementia after age 65
How Trivina should be stored
Keep this medicine out of the sight and reach of children.
Store at a maximum of 25 °C.
Use before the expiry date stated on the carton or blister. The expiration date is the last day of the specified month.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
Trivina white tablet:
The active substance is estradiol valerate 2 mg.
Other ingredients are lactose monohydrate 86.6 mg, corn starch, gelatin, talc, and magnesium stearate.
Trivina blue tablet:
The active substances are estradiol valerate 2 mg, and medroxyprogesterone acetate 20 mg (MPA).
Other ingredients are lactose monohydrate 150 mg, corn starch, indigo carmine (dye E 132), gelatin, and magnesium stearate.
Trivina yellow tablet:
Other ingredients are lactose monohydrate 86.5 mg, corn starch, gelatin, yellow iron oxide (dye E 172), and magnesium stearate.
Appearance and package sizes of the medicine
White tablet: white or almost white, round, cupped with a score, marked T, Ø 7 mm.
Blue tablet: light blue or light blue dotted, round, flat with a score, beveled edge, Ø 9 mm.
Yellow tablet: yellow, round, flat with a score, beveled edge, Ø 7 mm.
Packaging: Blister cards with 70 white, 14 blue, and 7 yellow tablets, 1 x 91 pieces.
Marketing Authorisation Holder:
Orion Corporation
Orion Indie 1
FI-02200 Espoo
Finland
Manufacturer:
Orion Corporation Orion Pharma
Orion Indie 1
FI-02200 Espoo
Finland