0.5 mg and 1 mg gel
Estradiol
1. What Divigel is and what it is used for
Divigel is a preparation used for hormonal substitution therapy ( HormoneReplacement Therapy, HRT ). It contains the female sex hormone estrogen.
Divigel is used to:
Relieve symptoms during and after menopause
When menstruation ends ( menopause ), the woman’s estrogen drops. It can cause discomfort such as a feeling of warmth on the face, neck, and breasts (“hot flashes”). Divigel relieves these symptoms after menopause. Divigel should only be used if the problems cause problems in daily life.
Talk to your doctor if you do not feel better or if you feel worse.
2. What you need to know before using Divigel
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 an 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.
Check your breasts regularly to detect changes (see “Breast Cancer” below).
Perform regular breast examinations according to your doctor’s recommendations.
Do not use Divigel :
If any of the following applies to you. If you are not sure, talk to your doctor before taking Divigel.
Do not use Divigel:
-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 treated for it.
-If you have or have had a blood clot in a vein (venous thromboembolism ), in your legs (deep vein thrombosis ), or 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 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 Divigel, stop taking Divigel and contact your doctor immediately.
Warnings and cautions
-Talk to your doctor or pharmacist before using Divigel. 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 Divigel. 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 have 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 any close relative has had breast cancer or other estrogen-dependent cancer.
-high blood pressure
liver disease eg liver adenoma (benign tumor )
– diabetes
gallstones
-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 a hearing loss)
– hypertriglyceridemia (elevated blood lipids)
fluid accumulation due to heart or kidney disease
Hereditary angioedema (a rare, hereditary disease with painful swelling of the skin, mucous membranes of the gastrointestinal tract or respiratory tract)
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 use Divigel”.
-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 be headache, fatigue, or dizziness)
-If you get migraine-like headaches for the first time
-If you get pregnant
-If you get symptoms of blood clots, like
• painful swelling and redness of the legs
• sudden chest pain
• difficulty breathing
For further information, see below “Blood clots in a vein ( thrombosis )”
Note : Divigel 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 use
The use of HRT with estrogen alone increases the risk of severe thickening of the uterine lining and cancer of the uterine lining.
By taking progestogen as a supplement to estrogen for at least 12 days in each 28-day cycle, you are protected against this extra risk. The doctor will prescribe the progestogen if you have your uterus left. If your uterus has undergone surgery ( hysterectomy ), you should consult your doctor if you can take the medicine without t a progestogen.
For women with the uterus left who do not take HRT, an average of 5 out of 1,000 women aged 50-65 will be diagnosed with endometrial cancer.
For women aged 50-65 who have the uterus left and who take HRT with estrogen alone, between 10 and 60 women out of 1,000 users will be diagnosed with endometrial cancer (ie between 5 and 55 extra cases), depending on dose one and how as long as it is taken.
Irregular bleeding
If your doctor has prescribed progestogen tablets in addition to Divigel, you will usually have to bleed once a month (so-called dropout bleeding). But if you get unexpected bleeding or splashing bleeding in addition to your monthly bleeding and these:
– lasts longer than 6 months
– starts after taking Divigel for 6 months
– continues after you have stopped using Divigel
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 :
Retractions or pits
Changes in the nipple
Tubers that you can see or feel.
It is also recommended that you participate in a mammography examination when you are called to it. 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 combineestrogen-progestogenen 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 / m2)
-You have or have had 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 leg, lu, ng another 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, an average of 4-7 out of 1,000 people are expected to have a blood clot in a vein over a 5-year period.
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)
For women in their 50s without a uterus who take estrogen alone for more than 5 years, 5 – 8 out of 1,000 users are expected to get a blood clot in a vein (ie 1 extra case).
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. For women without a uterus who take estrogen alone, there is no increased risk of developing heart disease.
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.
Women with a tendency to discolour the skin (chloasma) should minimize exposure to sun or ultraviolet radiation when using Divigel.
Other medicines and Divigel
Other medicines and Divigel
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription. This also applies to over-the-counter medicines, herbal medicines, or other natural products.
Some medicines can affect the effect of Divigel, which can lead to irregular bleeding. The following applies:
– Medicines for epilepsy (eg phenobarbital, phenytoin and carbamazepine)
-Trugs against tuberculosis (eg rifampicin, rifabutin)
-Läkemedel against HIV – infection (for example, nevirapine, efavirenz, ritonavir, and nelfinavir)
-Natural medicine containing St. John’s wort (Hypericum perforatum)
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 Divigel as it may affect the results of some tests.
Pregnancy, breastfeeding and fertility
Divigel is intended for women whose menstruation has stopped. If you become pregnant, stop taking Divigel and consult a doctor.
Driving and using machines
No studies have been performed on the effect of Divigel on the ability to drive or use machines.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires increased attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effect and/or side effects . Descriptions of these effects and side effects can be found in other sections. Therefore, always read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Divigel contains propylene glycol
Divigel contains propylene glycol , which may cause skin irritation.
3. How to use Divigel
Always use Divigel exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.
When you can start using Divigel
You can start using Divigel immediately if:
-You have never used hormone replacement therapy before
-You are switching from a hormone replacement drug that does not cause menstruation
Wait until your period ends if:
-You switch from another type of hormone replacement drug that causes menstruation
If you have not had your uterus removed, your doctor will normally also prescribe medicine containing progestogen. This is usually a tablet that you take 12-14 days during each monthly cycle. After each period of progestogen, you will usually have a bleeding period, such as a menstrual period.
How much to use
Divigel is available in single-dose containers containing 0.5 mg estradiol in 0.5 gram gel or in single-dose containers containing 1 mg estradiol in 1 gram gel.
-Each package of Divigel 0.5 mg gel single-dose container contains only 0.5 mg.
-Each package of Divigel 1 mg gel single-dose container contains only 1 mg.
Use the amount of Divigel gel prescribed by your doctor. Your doctor will strive to prescribe the lowest effective dose to treat your symptoms in the shortest possible time. Talk to your doctor if you think dose one is too strong or not strong enough.
– The usual dose is between 0.5 mg and 1.5 mg estradiol per day.
-Use the following 0.5 mg or 1 mg single-dose container, depending on the dose and package size prescribed by your doctor.
For a daily dose of 0.5 mg: Use a 0.5 g single-dose container
For a daily dose of 1 mg: There are two options. Use 1 g single-dose container or use two 0.5 g single-dose containers.
For a daily dose of 1.5 mg: There are two options. Use three 0.5 g single-dose containers or
use a 0.5 g single-dose container and a 1 g single-dose container.
If you are also taking tablets with progestogens , take them as recommended by your doctor. You will usually experience a loss of bleeding after each period of progestogen .
How to apply gel one
Divigel should be gently applied to dry and cleansed skin. The drug should not be swallowed.
Where to apply gel one
-Do not apply gel to your breasts, face or irritated skin.
-Apply gel one on the lower part of your body or thighs.
-Apply gel one on different sides of the body every day.
Follow these instructions:
1.Applicera gel is a once-a-day to the skin on the lower part of your body or thighs.
Spread the gel on a surface 1-2 times the size of your hand
Let the gel dry for a few minutes.
4. Wash your hands after applying the gel. Avoid getting the gel in your eyes. Gel one can irritate your eyes.
5. Do not wash the skin where you have applied the gel for the next hour.
If you need surgery
If you are going to have an operation, tell your surgeon that you are taking Divigel. You may need to stop taking Divigel for 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, “Blood clots in a vein ( thrombosis )”). Ask your doctor when it is appropriate to start taking Divigel again.
If you use more Divigel gel than you should
If you have ingested too much medicine or if e.g. If a child has inadvertently ingested the medicine, contact a doctor, hospital, or the Poison Information Center for risk assessment and advice. You may feel flatulence (gas), feel anxious or irritated, or your breasts may ache. Nausea, vomiting, and bleeding can also occur in some women. Overdose is unlikely with transdermal application (use on the skin). The treatment consists of treating the symptoms. Gel one should be washed off. The symptoms disappear when the treatment is stopped or when the dose is reduced.
If you have swallowed Divigel
If you have swallowed Divigel, there is nothing to worry about. But you should inform your doctor.
If you forget to use Divigel
-Apply the missed dose one when you remember it if you are not more than 12 hours late.
-If you are more than 12 hours late, you can ignore the forgotten dose one.
-Remembering your dose can cause bleeding between your periods. This is called breakthrough bleeding.
If you stop using Divigel
Continue to use your medicine according to your doctor’s instructions. Keep using Divigel even if you seem to be getting better. If you quit too soon or quit too suddenly, your problem may return.
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.
Stop using gel one and see a doctor immediately if you notice any of the following serious side effects are :
-your blood pressure will be elevated
-your skin or whites of the eyes turn yellow (jaundice)
-you suddenly get a migraine-like headache (see section 2)
-you get signs of a blood clot (see section 2)
-you get one of the diseases/problems
listed in section 2.
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
• Probable memory loss, if treatment with HRT is started after the age of 65
See section 2 for more information on these side effects .
During the first months of treatment, breakthrough bleeding, spotting, and breast tenderness or breast enlargement may occur. These are usually temporary and usually disappear with continued treatment.
Other side effects:
Common (may affect up to 1 in 10 people)
– itchy skin, rash, pain, sweating, swollen feet and swelling of the lower legs
-breasts become sore or painful
-weight gain or weight loss
-headache, dizziness
– abdominal pain, nausea or nausea, bloating
-blotting or spotting, menstrual disorders
-depression, nervousness, listlessness,
hot flashes
Uncommon (may affect up to 1 in 100 people)
-change of sexual desire and mood, anxiety, insomnia, apathy , emotional instability, impaired concentration, elation, agitation
– migraine, delusion, tremors
-impaired vision, dry eyes
-high blood pressure, superficial phlebitis, purpura
shortness of breath, rhinitis
benign breast or uterine tumor
-increased appetite, high cholesterol levels in the blood
-increased heart rate
-constipation, indigestion, diarrhea, rectal problems
– acne, alopecia, dry skin, nail problems, skin nodules, excessive hair growth,, hives (increased itchy rash on the skin), painful red skin nodules (erythema nodosum)
joint pain, muscle cramps
-increased urination frequency/urination, loss of bladder control, urinary tract infection, discoloration of urine, hematuria
-saint or swollen breasts, abnormal growth of the uterine lining, uterine problems
fatigue, abnormal laboratory values, weakness, fever, flu-like symptoms, general malaise
-allergic reactions ( hypersensitivity reactions )
Rare (may affect up to 1 in 1,000 people)
-venous thromboembolism (blood clot)
-hepatic effects and bile effects
-sensitivity to contact lenses
-period pain
-pre-mentally-like syndrome
Side effects reported after market introduction with unknown frequency (cannot be calculated from the available data)
-uterine fibroids (benign tumors in the uterus)
hereditary angioedema (rare, hereditary disease with painful swelling of the skin, the lining of the gastrointestinal tract, or the respiratory tract)
-cerebral circulatory disorder
bloating
liver disease that causes yellowing skin
contact rash, eczema
If you experience any of these side effects is to inform your doctor. Your doctor will decide if you should stop using the medicine for a while.
Dementia
Hormone replacement drugs do not prevent memory loss. There is some evidence of a higher risk of memory loss in women who start using HRT after the age of 65. Talk to your doctor for advice.
The following side effects have been reported with other HRTs:
disease of the gallbladder
-believable dementia in patients over 65 years of age
-different skin diseases:
– dark skin spots, especially on the face and neck, so-called “pregnancy spots” (chloasma)
– erythema multiforme
purpura due to lack of density or function of vessels ( vascular purpura).
Reporting of side effects ar
If you get any side effects, talk to your doctor or pharmacist. This also applies to side effects that are not mentioned in this information. You can also report side effectsdirectly (see details below). By reporting side effects , you can help increase drug safety information.
The Medical Products Agency
Box 26
751 03 Uppsala
5. How to store Divigel
Keep out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and unit dose after EXP. The expiration date is the last day of the specified month
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. These measures will help to protect the environment.
6. Contents of the packaging and other information
What Divigel 0.5 mg gel and Divigel 1 mg gel contain:
-The active substance is estradiol. There is 0.5 mg (milligrams) or 1.0 mg of estradiol in each single-dose container.
The other ingredients are carbomer 974P, trolamine, propylene glycol, ethanol and purified water.
What the medicine looks like and contents of the pack
Divigel gel is an alcohol-based gel
-Divigel 0.5 mg gel is supplied in packs of 28 or 91 doses
-Divigel 1 mg gel is supplied in packs of 28 or 91 doses
-Everything pack sizes may not be marketed
Marketing Authorisation Holder:
Orion Corporation
Orionvägen 1
FI-02200 Espoo
Finland
Manufacturer :
Orion Corporation Orion Pharma
Tengströmsgatan 8
FI-20360 Turku
Finland
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 :
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