Iuvinelle

Leaflet accompanying the packaging: information for the patient

Juvinelle, 1 mg + 2 mg, tablets

Estradiol valerate + Dienogest

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Juvinelle and what is it used for
• 2. Important information before taking Juvinelle
• 3. How to take Juvinelle
• 4. Possible side effects
• 5. How to store Juvinelle
• 6. Contents of the pack and other information

1 What is Juvinelle and what is it used for

Juvinelle is a medicine used for hormone replacement therapy (HRT).
It contains two types of female hormones, estrogen and progestogen. Juvinelle is indicated for use in postmenopausal women, at least 12 months after their last natural menstrual period.
Juvinelle is used to relieve symptoms that occur after menopause.
During menopause, the amount of estrogen produced by the woman's body decreases.
This can lead to symptoms such as a feeling of heat on the face, neck, and chest (so-called hot flashes). Juvinelle relieves these symptoms (occurring after menopause). Juvinelle is prescribed only in cases where the symptoms significantly affect the patient's daily life.

2 Important information before taking Juvinelle

Medical history and regular check-ups

Taking HRT is associated with a risk that should be considered when deciding to start or continue therapy.
Experience with the use of therapy in women with premature menopause (caused by ovarian failure or surgical procedures) is limited. In the case of women with premature menopause, the risk of taking HRT may be different. Consult your doctor.
Before starting (or re-taking) HRT, your doctor will take your medical history and that of your family. The doctor may perform a physical examination, including a breast examination and/or internal organs, if necessary.
After starting Juvinelle, you should regularly visit your doctor for check-ups (at least once a year). During these visits, you should discuss the benefits and risks of continuing to take Juvinelle with your doctor.
Follow your doctor's recommendations and have regular breast exams.

When not to take Juvinelle

If any of the following points apply to you, or if you have any doubts about any of the following points, you should consult your doctor before taking Juvinelle.
Do not take Juvinelle:

• if you currently have or have had breast cancer, or if there is a suspicion of it,
• if you have malignant tumors sensitive to estrogen, such as endometrial cancer, or if there is a suspicion of it,
• if you have vaginal bleeding of unknown cause,
• if you have untreated endometrial hyperplasia (thickening of the lining of the uterus),
• if you have or have had venous thromboembolic disease (deep vein thrombosis, e.g., of the legs or lungs, e.g., pulmonary embolism),
• if you have blood clotting disorders (such as protein C, protein S, or antithrombin deficiency),
• if you have or have recently had a disease caused by arterial thrombosis, such as a heart attack, stroke, or angina pectoris,
• if you have or have had liver disease and your liver test results have not returned to normal,
• if you have a rare, inherited blood disorder called porphyria,
• if you are allergic to estrogens, progestogens, or any of the other ingredients of this medicine (listed in section 6).

If any of the above factors occur for the first time while taking Juvinelle, you should stop taking the medicine immediately and contact your doctor.

Warnings and precautions

Before taking Juvinelle, discuss it with your doctor or pharmacist.
Tell your doctor if you currently have or have had any of the following conditions, as they may recur or worsen during treatment with Juvinelle. In such cases, you should be monitored more closely:

• uterine fibroids,
• endometriosis or previous cases of endometrial hyperplasia,
• increased risk of thromboembolic disorders or a history of them (see section 2 "Blood clots in the veins (thrombosis)"),
• increased risk of estrogen-sensitive tumors (e.g., if your mother, sister, or grandmother had breast cancer),
• high blood pressure,
• liver function disorders, such as a benign liver tumor,
• diabetes,
• gallstones,
• migraine or severe headaches,
• an immune system disease that affects many organs in the body (systemic lupus erythematosus, SLE),
• epilepsy,
• asthma,
• a disease that affects the eardrum and hearing (otosclerosis),
• very high levels of fats (triglycerides) in the body,
• fluid retention due to heart or kidney problems,
• inherited and acquired angioedema.

Stop taking Juvinelle and contact your doctor immediately

If you notice any of the following symptoms while taking HRT:

• any of the conditions listed in section 2 "When not to take Juvinelle",
• yellowing of the skin or whites of the eyes (jaundice) or liver function disorders,
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, with difficulty breathing, which suggest angioedema,
• significant increase in blood pressure (possible symptoms include headaches, fatigue, dizziness),
• migraine-like headaches that occur for the first time,
• pregnancy,
• signs of a blood clot, such as:
• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing. More information is available in section 2 "Blood clots in the veins (thrombosis)".

Note:Juvinelle is not a contraceptive. If it has been less than 12 months since your last menstrual period or if you are under 50 years old, you may need additional contraceptive measures. Consult your doctor.

HRT and cancer

Endometrial hyperplasia (thickening of the lining of the uterus) and endometrial cancer (cancer of the lining of the uterus)

Taking only estrogen HRT increases the risk of endometrial hyperplasia and endometrial cancer. The presence of progestogen in Juvinelle protects against this additional risk.

Irregular bleeding

Irregular bleeding or spotting may occur during the first 3 to 6 months of taking Juvinelle.
If, however, irregular bleeding:

• lasts longer than the first 6 months
• occurs when you have been taking Juvinelle for more than 6 months
• continues after stopping Juvinelle, you should see your doctor immediately.

Breast cancer

Data confirm that taking hormone replacement therapy (HRT) in the form of a combination of estrogen and progestogen or estrogen alone increases the risk of breast cancer. The additional risk depends on how long you take HRT. This additional risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or longer if HRT lasted more than 5 years.
Comparison
In women aged 50-54 who do not take HRT, breast cancer will be diagnosed in approximately 13-17 out of 1000 women over a 5-year period.
In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 patients (i.e., 0-3 additional cases).
In women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 out of 1000 patients (i.e., 4-8 additional cases).
In women aged 50-59 who do not take HRT, breast cancer will be diagnosed in approximately 27 out of 1000 women over a 10-year period.
In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 patients (i.e., 7 additional cases).
In women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 out of 1000 patients (i.e., 21 additional cases).

Have your breasts checked regularly. Contact your doctor if you notice any changes such as:

• indentations in the skin,
• changes in the breast area,
• any visible or palpable thickening.

In addition, it is recommended to participate in screening mammography if it is offered. When undergoing screening mammography, it is essential to inform the medical staff performing the X-ray that you are taking HRT, as this medicine may increase breast density, which can affect the mammography result. In the case of increased breast density, mammography may not detect all tumors.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that includes only estrogens or a combination of estrogens and progestogens is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, in women aged 50-54 who do not take HRT, ovarian cancer will be diagnosed over a 5-year period in approximately 2 out of 2000 women.
In women who have taken HRT for 5 years, it will occur in approximately 3 out of 2000 women taking it (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in the veins (thrombosis)

The risk of developing venous thromboembolic disease is about 1.3 to 3 times higher in women taking HRT, especially in the first year of treatment, than in women who do not take it.
Blood clots can be dangerous. If a clot gets into the lungs, it can cause chest pain, shortness of breath, fainting, or even death.
The likelihood of blood clots in the veins increases with age and depends on the presence of the following factors. Inform your doctor if any of the following situations occur:

• you are unable to walk for a long time due to extensive surgery, injury, or illness (see also section 3 "If surgery is necessary"),
• you are obese (body mass index BMI > 30 kg/m),
• you have blood clotting disorders and require long-term treatment with anticoagulant medication,
• any of your close relatives have had a blood clot in a leg, lung, or other organ,
• you have systemic lupus erythematosus (SLE),
• you have cancer.

Information about the symptoms of a blood clot can be found in section 2 "Stop taking Juvinelle and contact your doctor immediately".
Comparison
In women aged 50-59 who do not take HRT, a venous thrombosis will occur in approximately 4-7 out of 1000 women over a 5-year period.
In women aged 50-59 who have taken combined estrogen-progestogen HRT for more than 5 years, a venous thrombosis will occur in 9-12 out of 1000 women (i.e., 5 additional cases).

Heart disease (heart attack)

There is no scientific evidence that HRT can prevent heart attacks.
Women over 60 years old who take combined estrogen-progestogen HRT are slightly more likely to develop heart disease than those who do not take HRT.

Stroke

The risk of stroke is about 1.5 times higher in people taking HRT than in those who do not take it.
The number of additional stroke cases due to HRT increases with age.
Comparison
In women aged 50-59 who do not take HRT, a stroke will occur in approximately 8 out of 1000 women over a 5-year period. In women aged 50-59 who take HRT, a stroke will occur in 11 out of 1000 women over a 5-year period (i.e., 3 additional cases).

Other conditions

HRT does not prevent memory loss. There is evidence of an increased risk of memory loss in women who start HRT at an age above 65. Consult your doctor.

Juvinelle and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.
Some medicines may affect the action of Juvinelle. This can lead to irregular bleeding. This applies to the following medicines:

• medicines used to treat epilepsy (such as phenobarbital, phenytoin, and carbamazepine),
• medicines used to treat tuberculosis (such as rifampicin, rifabutin),
• medicines used to treat HIV infection (such as nevirapine, efavirenz, ritonavir, and nelfinavir),
• herbal products containing St. John's Wort (Hypericum perforatum)

HRT may affect the action of other medicines:

• an antiepileptic drug (lamotrigine), as it may increase the frequency of seizures
• Treatment regimens for combined hepatitis C virus (HCV) infection using ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, or using glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir may cause increased liver enzyme levels in blood tests in women taking combined hormonal contraceptives containing ethinyl estradiol. Juvinelle contains estradiol valerate instead of ethinyl estradiol. It is not known whether increased liver enzyme levels may occur when taking Juvinelle with such a treatment regimen for HCV infection. Your doctor will provide you with appropriate guidance.

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take, including those that are available without a prescription, herbal products, or other natural products.

Lab tests

If a blood test is necessary, inform the laboratory staff that you are taking Juvinelle, as it may affect the results of some tests.

Pregnancy and breastfeeding

Juvinelle is intended for use in postmenopausal women only. If you become pregnant, stop taking the medicine and contact your doctor.

Driving and using machines

No effects of Juvinelle on the ability to drive or use machines have been observed.

Juvinelle contains lactose

If you have been diagnosed with intolerance to some sugars, contact your doctor before taking the medicine.

3 How to take Juvinelle

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.
Your doctor will prescribe the lowest dose necessary to treat your symptoms for the shortest possible time. If you think the effect of the medicine is too weak or too strong, tell your doctor.

• Take one tablet daily, preferably at the same time.
• Swallow the tablet whole with water.
• Juvinelle can be taken with or without food.
• Start the next calendar pack the day after finishing the current one.
• Do not take breaks between packs.

If you are taking another HRT medicine

Continue taking your current medicine until you finish the pack and have taken all the tablets for that month. Take the first tablet of Juvinelle the next day. Do not take a break between the medicine you are currently taking and Juvinelle.

If you have been taking HRT with a weekly break

Start the pack the day after the break ends.

If you are taking HRT for the first time

You can start taking Juvinelle on any day.

Taking more than the recommended dose of Juvinelle

If you take more than the recommended dose of Juvinelle, you may experience nausea, vomiting, or bleeding from the genital tract. There is no need for any treatment, but if you are unsure, consult your doctor or pharmacist.

Missing a dose of Juvinelle

If you forget to take a tablet and it has been less than 24 hours since you should have taken it, take it as soon as possible. Take the next tablet at the usual time.
If more than 24 hours have passed since you should have taken the tablet, leave the missed tablet in the pack. Take the next tablets daily at the usual time. Do not take a double dose to make up for the missed dose.
Missing a tablet for several days may cause bleeding.

Stopping Juvinelle

Menopausal symptoms may recur, including hot flashes, difficulty sleeping, nervousness, dizziness, or vaginal dryness. After stopping Juvinelle, bone loss will resume.

If surgery is necessary

If you are scheduled for surgery, inform your surgeon that you are taking Juvinelle. It may be necessary to stop taking Juvinelle about 4-6 weeks before the planned surgery to reduce the risk of blood clots (see section 2 "Blood clots in the veins (thrombosis)"). Ask your doctor when you can resume taking Juvinelle.
If you have any further doubts about taking this medicine, consult your doctor or pharmacist.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
In the first few months of therapy with Juvinelle, irregular bleeding may occur. It usually has a temporary character and disappears as treatment continues. If the bleeding does not stop, contact your doctor.
The following diseases occur more frequently in women taking HRT than in those who do not:

• breast cancer,
• abnormal growth or malignant tumor of the endometrium (endometrial hyperplasia or endometrial cancer),
• ovarian cancer,
• blood clots in the veins of the legs or lungs (venous thromboembolism),
• heart disease,
• stroke,
• risk of memory loss, if HRT is started at an age above 65.

More information about the above side effects can be found in section 2 "Important information before taking Juvinelle".
The following side effects have been reported with Juvinelle:

Common (may affect up to 1 in 10 people)

• headache,
• nausea,
• breast tenderness, vaginal bleeding, hot flashes.

Uncommon (may affect up to 1 in 100 people)

• weight gain,
• drowsiness, nervousness, loss of appetite leading to weight loss, aggression, depression,
• decreased libido, inability to achieve orgasm,
• dizziness, migraine, overactivity, tingling sensation,
• high blood pressure, venous thrombosis (symptom may be leg pain) (see also section 2 "Blood clots in the veins (thrombosis)"), nosebleeds,
• bloating, abdominal pain, constipation, diarrhea, dry mouth, vomiting,
• gallbladder pain,
• increased sweating, acne, itching, dry skin with red, flaky areas (psoriasis),
• muscle pain, leg cramps,
• disorders of the uterine lining, painful menstruation, genital itching,
• vaginal thrush,
• fatigue, generalized fluid retention, facial swelling,
• edema.

Other side effects have been reported with HRT:

• gallbladder disease,
• various skin disorders:
• skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma),
• painful red skin nodules (erythema nodosum),
• a rash with blisters or redness resembling a target (erythema multiforme).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5 How to store Juvinelle

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging and blister after "Expiry date" or "EXP". The expiry date refers to the last day of the month stated.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6 Contents of the pack and other information

What Juvinelle contains

• The active substances of Juvinelle are estradiol valerate and dienogest. One tablet contains 1 mg of estradiol valerate (equivalent to 0.76 mg of estradiol) and 2 mg of dienogest.
• The other ingredients are: lactose monohydrate, cornstarch, povidone (K 25), magnesium stearate, colloidal anhydrous silica, red iron oxide (E172).

What Juvinelle looks like and contents of the pack

Juvinelle is a pinkish, round tablet with a diameter of 6 mm.
Calendar packs in blisters containing 28 and 3 x 28 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

DR. KADE Pharmazeutische Fabrik GmbH
Rigistrasse 2
12277 Berlin
GermanyKadefarm Sp. z o.o.
Sierosław, ul. Gipsowa 18
62-080 Tarnowo Podgórne, Poland
Tel.: + 48 61 862 99 43
e-mail: kadefarm@kadefarm.pl

Date of last revision of the leaflet:

Detailed information about this medicine is available on the website www.urpl.gov.pl.