Active ingredients: Didrogesterone
DUFASTON 10 mg film-coated tablets
Why is Dufaston used? What is it for?
Meaning of Dufaston
DUFASTON contains a medicine called dydrogesterone.
- Dydrogesterone is a synthetic hormone.
- It is very similar to the progesterone hormone produced by the body.
- Medicines like Dufaston are called progestins.
What Dufaston is used for
Dufaston can be taken alone or with estrogen. You may also be taking an estrogen depending on why you are taking Dufaston.
Dufaston is used:
- To treat symptoms of menopause (this treatment is called hormone replacement therapy or HRT)
- These symptoms vary from woman to woman.
- They can include hot flashes, night sweats, sleep disturbances, vaginal dryness and urinary symptoms.
- For problems that occur when the body doesn't make enough progesterone:
- Threat of abortion and habitual abortion
- Infertility due to low progesterone levels
- Dysmenorrhea (painful menstruation)
- Endometriosis (when tissue of the uterine lining grows outside the uterus)
- Irregular menstrual cycles
- Secondary amenorrhea (absence of menstruation before menopause)
- Functional menometrorrhagia (excessive blood loss during menstruation or blood loss outside of periods).
How Dufaston Works
The body normally balances the amount of the natural hormone progesterone with estrogen (the other main female hormone). If the body does not produce enough progesterone, Dufaston supplements it and restores the balance.
Your doctor may ask you to take estrogen along with Dufaston. This depends on why you are taking Dufaston.
For some women who use HRT, taking estrogen alone can cause abnormal thickening of the lining of the womb. This can happen even if you do not have a uterus and have a history of endometriosis. Taking dydrogesterone for part of the monthly cycle helps prevent thickening of the lining of the uterus.
Contraindications When Dufaston should not be used
Do not use DUFASTON:
- if you are hypersensitive to the active substance or to any of the other ingredients of Dufaston
- if you have ever had vaginal bleeding, the cause of which is unknown
- if you have or are suspected of having a progestogen-dependent tumor (the growth of which is sensitive to progestogens) such as a brain tumor called meningioma
- and have or have had breast cancer or are suspected of having it
- if you have excessive thickening of the womb wall (endometrial hyperplasia) which is not being treated
- if you have or have ever had a blood clot in a vein (thrombosis) in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism)
- if you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency)
- if you have or have recently had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina
- if you have or have ever had liver disease and your liver function tests have not returned to normal
- if you have a rare blood disorder called "porphyria" which is passed down in the family (inherited)
Do not take Dufaston if you have any of the above. If you are not sure, talk to your doctor or pharmacist before taking Dufaston. If any of the above conditions appear for the first time while using Dufaston, stop taking it immediately and consult your doctor immediately.
If you are taking Dufaston together with an estrogen, for example as part of HRT, please read the 'Do not use' section in the package leaflet of the estrogen you are taking.
Precautions for use What you need to know before taking Dufaston
Tell your doctor if you have or have ever had any of the following problems before starting treatment as these may come back or get worse during treatment with Dufaston. If this occurs, you should see your doctor more often for a check-up:
- fibroids inside the uterus
- growth of the uterine wall outside the uterus (endometriosis) or a history of overgrowth of the uterine wall (endometrial hyperplasia)
- increased risk of developing blood clots (see "Blood clots in a vein [thrombosis]")
- increased risk of having estrogen-sensitive cancer (resulting from having a mother, sister or grandmother with breast cancer)
- high blood pressure
- liver disorder, such as a benign liver tumor
- diabetes
- gallstones
- migraine or severe headache
- a disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE)
- epilepsy
- asthma
- a disease affecting the eardrum and hearing (otosclerosis)
- a very high level of fat in the blood (triglycerides)
- water retention due to heart or kidney problems
Stop taking Dufaston and see a doctor immediately if you notice any of the following effects while taking HRT: - any of the conditions listed in the "Do not use Dufaston" section
- yellowing of the skin or whites of the eyes (jaundice). These can be signs of a liver disease a
- noticeable increase in blood pressure (symptoms may be headache, tiredness, dizziness)
- migraine-like headache occurring for the first time
- pregnancy
- if you notice signs of a blood clot, such as:
- painful swelling and redness of the legs
- sudden chest pain
- difficulty in breathing.
- For more information, see "Blood clots in a vein (thrombosis)".
Children and adolescents
The use of Dufaston in girls before their first menstruation is not indicated. The efficacy and tolerability of Dufaston in adolescents between 12 and 18 years is not known.
Take special care with Dufaston:
If you have to take Dufaston for abnormal bleeding, your doctor will need to investigate the cause of the bleeding before starting therapy with this drug. If you experience unexpected bleeding or a little blood loss this is usually nothing to worry about. This is more likely to happen during the first few months of Dufaston therapy.
However, schedule a visit with your doctor right away if the bleeding or small blood loss:
- continues beyond the first few months
- starts after it has been on treatment for some time
- it continues even after stopping treatment. This may be a sign that the lining of the womb is getting thicker. Your doctor will need to investigate the cause of the bleeding or small blood loss and may perform a test to look for cancer of the lining of the womb.
Before taking Dufaston, check with your doctor or pharmacist if you have any of the following conditions:
- depression
- liver problems
- a rare inherited blood problem called "porphyria".
If you have any of the above conditions (or you are not sure) talk to your doctor or pharmacist before taking Dufaston. It is especially important to report if the conditions listed have worsened during pregnancy or previous hormone therapies. Your doctor may decide to monitor you more closely during treatment. If you notice any worsening or returning of the listed conditions while taking Dufaston, your doctor may stop the treatment.
Dufaston and HRT
Along with the benefits, HRT has some risks that you and your doctor will need to consider when deciding to take this treatment. If you are taking Dufaston with estrogen as part of HRT, the following information is important. Also read the information in the package leaflet of the estrogen you are taking.
Premature menopause
There is limited evidence on the risks of HRT used to treat early menopause. There is a low level of risk in young women. This means that the balance of benefits and risks for young women taking HRT for early menopause may be better than in older women.
Medical checks
Before starting or restarting HRT, your doctor will ask you about your personal and family medical history and may decide to examine your breasts or pelvis (lower abdomen).
Before and during treatment, your doctor may do screening tests such as mammography (an X-ray of the breast). He will tell you how often to take these tests. Once you have started taking Dufaston, you will need to see your doctor for regular check-ups (at least once a year).
Endometrial cancer and endometrial hyperplasia
Women who have a uterus and take estrogen-only HRT for a long time have a higher risk of:
- endometrial cancer (cancer of the lining of the womb)
- endometrial hyperplasia (altered thickness of the uterine lining)
Taking Dufaston with estrogen (for at least 12 days in a 28 day cycle) or as a continuous combined estrogen-progestogen therapy can prevent this additional risk.
Breast cancer
Women who take estrogen-progestogen HRT, and possibly estrogen-only HRT, have an increased risk of breast cancer. The risk depends on how long HRT is taken. The additional risk becomes evident after about 3 years. However, it returns to normal 5 years after stopping treatment. Be sure to:
- have regular breast checks (your doctor will tell you how often)
- check your breasts regularly for changes such as:
- depressions of the skin
- nipple variations
- any visible or perceptible hardening.
If you notice any changes, see your doctor right away.
Ovarian cancer
Ovarian cancer is very rare but serious. It is difficult to diagnose. This is often due to the absence of noticeable symptoms of the disease. Taking estrogen-only HRT for over 5 years may slightly increase the risk of ovarian cancer. Some studies suggest that prolonged use of estrogen-progestogen HRT may have the same risk. (or slightly lower).
Blood clots in a vein (thrombosis)
HRT increases the risk of venous thrombosis. The risk increases up to three times that of the population not taking HRT. The risk is greatest in the first year of treatment. You are more likely to get thrombosis if:
- she is older
- has cancer
- is very overweight
- you are taking an estrogen
- are pregnant or have recently had a baby
- you (or close relatives) have previously had thrombosis which may have affected the legs or lungs
- is immobilized for a long time for surgery, trauma or illness (see also Operations)
- have a disease called "systemic lupus erythematosus" (SLE) - a disease that causes joint pain, rash and fever.
If you have any of the above conditions (or you are not sure) ask your doctor if you can take HRT.
If you feel swollen and painful legs, sudden chest pain or difficulty breathing:
- see a doctor immediately
- do not take HRT again until your doctor tells you to continue.
These may be symptoms of venous thrombosis.
Also tell your doctor or pharmacist if you are taking medicines to prevent thrombosis (blood thinners) such as warfarin. Your doctor will need to pay particular attention to the benefits and risks of taking HRT.
Operations
If you have surgery planned, tell your doctor before surgery that you are taking HRT. Do it long before the surgery. You may need to stop taking HRT a few weeks before the operation. In some cases you may need some other treatment before and after the operation. Your doctor will tell you when to start taking HRT again.
Heart disease
HRT does not help prevent heart disease. Women who take estrogen-progestogen HRT have a slightly increased risk of developing heart disease compared to those who do not. The risk of heart disease also increases with age. The number of additional cases of heart disease due to estrogen-progestogen HRT is very low in healthy women who have recently been through menopause. The number of additional cases increases with age.
If you experience chest pain that spreads to your arm or neck:
- see a doctor immediately
- do not take HRT again until your doctor tells you to continue.
Pain could be a symptom of heart attack.
Stroke
Taking estrogen-progestogen or estrogen-only HRT increases the risk of having a stroke. The risk increases up to one and a half times that of the population not taking HRT. The comparative risk between users and non-users does not change with each other. "age or time since menopause. The risk of stroke increases with age. This means that the overall risk of stroke in women taking HRT increases with age. If you experience an "unexplained and severe headache or migraine (with or without vision problems):
- see a doctor immediately
- do not take HRT again until your doctor tells you to continue.
This could be an early symptom of a stroke.
Other conditions
HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women starting HRT after the age of 65. Talk to your doctor for advice
Interactions Which drugs or foods may change the effect of Dufaston
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription and herbal preparations.
In particular, tell your doctor or pharmacist if you are taking the following medications.
These drugs can reduce the effect of Dufaston and cause bleeding or small blood loss:
- herbal preparations containing St. John's wort, valerian root, sage or gingko biloba
- drugs for epilepsy such as phenobarbital, phenytoin, carbamazepine
- medicines for infections such as rifampicin, rifabutin, nevirapine, efavirenz
- AIDS drugs such as ritonavir, nelfinavir.
If you take any of these medications (or are not safe) talk to your doctor or pharmacist before taking Dufaston.
Dufaston with food and water
DUFASTON can be given regardless of food intake
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Pregnancy
There may be an increased risk of hypospadias (a birth defect of the penis involving urinary opening) in children whose mothers have taken certain progestogens. However, this increased risk is not yet certain. To date, there is no evidence that taking dydrogesterone during pregnancy is dangerous. Over 10 million pregnant women have taken Dufaston.
- Talk to your doctor before taking Dufaston if you are pregnant.
- If you become pregnant or think you may be, consult your doctor. He will discuss with you the benefits and risks of taking Dufaston during pregnancy.
Feeding time
If you are breast-feeding, do not take Dufaston. It is not known if Dufaston passes into breast milk and affects the baby. Studies with other progestogens show that a small amount of them passes into breast milk.
Fertility
There is no evidence that didrogesterone reduces fertility when taken as recommended by the physician
Driving and using machines
You may feel sleepy or dizzy after taking Dufaston. This is most common in the first few hours after taking. If this happens, do not drive or use machines. Wait to see how Dufaston affects you before driving or using machines.
Important information about some of the ingredients of Dufaston
Dufaston contains milk sugar (lactose). If you know that you cannot tolerate or digest some sugars (that you have an "intolerance to some sugars), talk to your doctor before taking the drug. This may relate to rare inherited conditions that affect how the body uses lactose such as" deficiency of lactose. Lapp lactase "or" glucose-galactose malabsorption ".
Dose, Method and Time of Administration How to use Dufaston: Posology
Dufaston should always be taken exactly as prescribed by your doctor. If you are not sure, check with your doctor or pharmacist. Your doctor will adjust the dose based on what is right for you.
Taking the drug
- Swallow each tablet with water.
- You can take the tablets with or without food.
- If you have to take more than one tablet, divide the intakes throughout the day. For example, take one tablet in the morning and one in the evening.
- Try to always take the tablets at the same time of the day. This ensures a constant amount of the drug in your body. This will also help you remember to take the tablets.
- The score line on the tablets only serves to facilitate breaking to aid swallowing. It cannot be used to take half of the tablet. How many tablets to take The number of tablets to take and for how long depends on why it is being treated. If you still have natural cycles, the first day of your period is when the bleeding starts. If you no longer have natural cycles, your doctor will decide when you start the first day of your cycle and when you should start taking the tablets.
To treat the symptoms of menopause
- If you are being treated with 'sequential' HRT (take an estrogen tablet or use a patch for all days of your period):
Take 1 tablet per day
Take the tablet in the last 14 days of the 28 day cycle.
- If you are being treated with 'cyclic' HRT (take an estrogen tablet or use a patch usually for 21 days followed by a treatment-free interval of 7 days):
Take 1 tablet per day
Take the tablet in the last 12-14 days of estrogen therapy.
- If necessary, your doctor may increase the dose to 2 tablets a day.
Threat of abortion:
- If you have never had a miscarriage before:
Take a dose of up to 4 tablets.
Then take 2 or 3 tablets a day until you have no more symptoms.
- Habitual abortion:
- If you have already had miscarriages:
Take 2 tablets a day.
Take the drug until the twelfth week of pregnancy.
Infertility due to low progesterone levels:
- Take 1 or 2 tablets a day.
- Take them from the second half of the cycle until the first day of the next cycle.
- The day you start therapy and the number of days you take the tablets will depend on the length of your cycle.
- Continue therapy for at least 3 consecutive cycles.
Dysmenorrhea (painful menstruation):
- Take 1 or 2 tablets a day.
- Take them only from the 5th to the 25th day of the cycle.
Endometriosis:
- Take 1 to 3 tablets per day.
- You may need to take the tablets:
All days of the cycle.
Only from the 5th to the 25th day of the cycle.
Irregular menstrual cycles:
- Take 1 or 2 tablets a day.
- Take them from the second half of the cycle until the first day of the next cycle.
- The day you start therapy and the number of days you take the tablets will depend on the length of your cycle.
Secondary amenorrhea (absence of menstruation before menopause):
- Take 1 or 2 tablets a day.
- Continue for 14 days during the second half of the theoretical cycle.
Functional menometrorrhagia (excessive blood loss during menstruation or blood loss out of periods)
- If treatment is to stop bleeding:
Take 2 or 3 tablets a day.
Continue for at least 10 days.
- For continuous treatment:
Take 1 or 2 tablets a day.
Continue for the second half of the cycle.
- The day you start therapy and the number of days you take the tablets will depend on the length of your cycle.
Overdose What to do if you have taken too much Dufaston
If you use more DUFASTON than you should
If you (or anyone else) have ingested an overdose of DUFASTON, this is unlikely to hurt you. No treatment is needed. If you are worried, contact your doctor.
If you forget to take Dufaston
- Take the forgotten tablet as soon as you remember. However, if it has already been more than 12 hours since you should have taken it, skip the missed dose and take the next one at the normal time.
- Do not take a double dose to make up for a forgotten dose.
- You may notice bleeding or slight blood loss if you miss a dose.
- If you stop taking Dufaston
Do not stop taking Dufaston without your doctor's advice.
Side Effects What are the side effects of Dufaston
Like all medicines, Dufaston can cause side effects, although not everybody gets them.
The following side effects may occur with this medicine:
Side effects when Dufaston is taken alone
Stop taking Dufaston and see your doctor immediately if you notice any of the following side effects:
- liver problems - the signs may include yellowing of the skin and whites of the eyes (jaundice), feeling tired, generally feeling unwell or stomach pain (affects less than 1 in 100 patients treated)
- allergic reactions - signs may include breathing difficulties or reactions involving the whole body such as feeling sick, nausea, diarrhea or low blood pressure (affecting less than 1 in 1000 patients treated)
- swelling of the skin of the face and neck which may cause breathing difficulties (affects less than 1 in 1000 patients treated) Stop taking Dufaston and see your doctor immediately if you notice any of the side effects listed above
Other side effects of Dufaston taken alone:
Common (affects less than 1 in 10 patients treated)
- headache, migraine
- nausea
- breast tension or pain
- irregular, heavy or painful periods
- absence of menstruation or less frequent menstruation than normal
Uncommon (affects less than 1 in 100 patients treated)
- weight gain
- dizziness
- depressed mood
- He retched
- allergic reactions such as skin rash, severe itching or hives;
- abnormalities in liver function, such as jaundice, malaise, abdominal pain
Rare (affects less than 1 in 1000 patients treated)
- drowsiness
- swelling of the breasts
- a type of anemia caused by the destruction of red blood cells
- swelling due to fluid buildup, often in the lower legs or ankles
- increase in the size of progestogen-sensitive tumors (such as meningioma).
Adverse events in younger patients are to be expected similar to those occurring in the adult population.
Side effects when Dufaston is taken with an estrogen (estrogen-progestagen HRT)
If you are taking Dufaston together with an estrogen please also read the package leaflet that accompanies the medicine containing estrogen. See also the section "Before using Dufaston" for more information on the side effects listed below.
Stop taking Dufaston and see your doctor immediately if you notice any of the following side effects:
- Swelling with pain in the legs, sudden chest pain or difficulty in breathing. These can be signs of thrombosis.
- Chest pain spreading to the arm and neck. It could be a sign of a heart attack.
- Unexplained severe headache or migraine (with or without vision problems). These could be signs of a stroke.
Stop taking this medicine and see your doctor immediately if you experience any of the above side events.
Schedule a visit to the doctor right away if you notice:
- Breast skin depressions, nipple changes, or any visible or noticeable hardening. These could be signs of breast cancer.
Other side effects from taking Dufaston with an estrogen include abnormal thickening or cancer of the lining of the womb or cancer of the ovaries.
If any of the side effects gets serious, or if you notice any side effects not described in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
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 after EXP. The expiry date refers to the last day of that month. Do not use this medicine if you notice visible signs of deterioration. Do not throw any medicine into the drinking water. discharge and in household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
CONTENTS OF THE PACKAGE AND OTHER INFORMATION
What Dufaston contains
The active ingredient is didrogesterone
- each film-coated tablet contains 10 mg of didrogesterone
The excipients of the core are: lactose, hypromellose, corn starch, colloidal silica, magnesium stearate
The excipient of the coating film is: Opadry white Y-1-7000 [hypromellose, Macrogol 400, titanium dioxide (E171)].
What Dufaston looks like and contents of the pack
The tablets are round, biconvex, scored, white, 7 mm in diameter, debossed with "155" on one side on both sides of the score.
- The tablets are packed in blisters consisting of aluminum foil and a PVC film.
- The pack contains 14 or 42 coated tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DUFASTON 10 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains
Active ingredient: 10 mg of didrogesterone.
Excipients: lactose
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
White, round, biconvex, scored film-coated tablet, debossed with "155" on one side on both sides of the score (size 7 mm).
The score line is only to facilitate breaking of the tablets to aid in swallowing and not to divide them into equal doses.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hormone replacement therapy
To balance the effects of estrogen on the endometrium in women with an intact uterus undergoing hormone replacement therapy for estrogen deficiency symptoms including those resulting from physiological or surgical menopause.
Insufficiency of progesterone
Treatment of cases of progesterone insufficiency that can occur in:
- Threat of abortion and habitual abortion
- Infertility due to insufficiency of the corpus luteum
- Dysmenorrhea
- Endometriosis
- Irregular cycles
- Secondary amenorrhea
- Functional menometrorrhagia
04.2 Posology and method of administration
The posology, treatment schedule and duration of treatment can be adapted according to the severity of the dysfunction and the clinical response.
Hormone replacement therapy
• Continuous Sequential Therapy: Estrogen is administered continuously and a 10 mg tablet of dydrogesterone is added on the last 14 days of each 28-day cycle, sequentially.
• Cyclic therapy: When estrogen is administered cyclically with a treatment-free interval, generally 21 days of treatment and 7 days of interruption. A 10 mg tablet of didrogesterone is added in the last 12-14 days of estrogen therapy.
• Based on the clinical response, the dose may subsequently be increased to 20 mg of dydrogesterone per day.
Threat of abortion: An initial dose of up to 40 mg of dydrogesterone can be given, followed by 20 or 30 mg per day until symptoms resolve.
Habitual abortion: 10 mg of didrogesterone twice daily until the 12th week of pregnancy.
Infertility due to insufficiency of the corpus luteum: 10 or 20 mg of didrogesterone per day from the second half of the menstrual cycle to the first day of the next cycle. Treatment should be continued for at least three consecutive cycles.
Dysmenorrhea: 10 or 20 mg of didrogesterone per day from the 5th to the 25th day of the menstrual cycle.
Endometriosis: 10 to 30 mg of didrogesterone per day from the 5th to the 25th day of the cycle or continuously.
Irregular cycles: 10 or 20 mg of didrogesterone per day from the second half of the menstrual cycle to the first day of the next cycle. The starting day and the number of treatment days will depend on the individual cycle length.
Secondary amenorrhea: 10 or 20 mg of didrogesterone per day, to be administered daily for 14 days during the second half of the theoretical menstrual cycle to produce an "optimal secretory transformation of the endometrium that has been adequately stimulated with endogenous or exogenous estrogens."
Functional menometrorrhagia: When starting treatment to stop a bleeding episode, 20 or 30 mg of dydrogesterone should be given daily for up to 10 days.
For continuous treatment, 10 or 20 mg of didrogesterone per day should be administered during the second half of the menstrual cycle. The starting day and the number of treatment days will depend on the individual cycle length.
Withdrawal bleeding occurs if the endometrium has been adequately stimulated by endogenous or exogenous estrogens.
There is no relevant use of dydrogesterone prior to menarche. The safety and efficacy of dydrogesterone in 12-18 year old adolescents have not been established. Currently available data are described in sections 4.8 and 5.1 but no recommendation on a posology can be made.
Method of administration
For oral use.
For the administration of higher doses the tablets should be taken evenly distributed throughout the day.
04.3 Contraindications
- Known hypersensitivity to the active substance or to any of the excipients
- Known, past or suspected breast cancer
- Known or suspected progestogen-dependent neoplasms. Genital bleeding of unknown origin
- Untreated endometrial hyperplasia
- Previous or current venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism)
- Known thrombophilic diseases (e.g. protein C, protein S or antithrombin deficiency, see section 4.4)
- Current or recent arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction)
- Acute liver disease or history of liver disease, until liver function tests have returned to normal
- Porphyria
04.4 Special warnings and appropriate precautions for use
Before starting treatment of abnormal bleeding with dydrogesterone, the etiology of the bleeding should be clarified.
Intermenstrual bleeding or minor bleeding may occur during the first months of treatment. If breakthrough bleeding or minor bleeding occurs after a period of treatment or continues after therapy has been stopped, the reason should be investigated and endometrial biopsy may be included to rule out endometrial cancer.
Conditions that require supervision
If any of the conditions listed below is present, has occurred in the past and / or has worsened during pregnancy or during previous hormonal treatments, the patient should be carefully monitored. Consideration should be given that these conditions may recur or worsen during treatment with dydrogesterone and that therapy should be discontinued.
- porphyria
- depression
- changes in liver function caused by acute or chronic liver disease
Other conditions
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The following warnings and precautions apply to the use of didrogesterone in combination with estrogen for hormone replacement therapy (HRT)
See also warnings and precautions listed for estrogen products.
For the treatment of postmenopausal symptoms, HRT should only be initiated if symptoms adversely affect quality of life. However, a careful assessment of the risks and benefits should be carried out periodically, at least annually, and HRT should only be continued if the benefits outweigh the risks.
There is limited evidence of risks associated with HRT for the treatment of early menopause. However, given the low level of absolute risk in young women, the benefit / risk ratio for these women may be more favorable than in older women.
Medical visits / checks
Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. On this basis, physical examination (including pelvic and breast) and evaluation of contraindications and warnings for use will be conducted. During the treatment, periodic checks are recommended with frequency and characteristics adapted to the individual needs of the woman. Patients should be advised to report changes in their breasts to their doctor or nurse (see under "Breast cancer"). Investigations, including appropriate imaging methods, such as mammography, should be conducted in accordance with the control programs currently in use, modified according to individual clinical needs.
Conditions that require special control
In the event that any of the following conditions is present, or has been present in the past and / or has been aggravated by pregnancy or previous hormonal treatment, the patient should be closely monitored. Take into consideration that these conditions may recur or worsen during treatment with Dufaston:
• Leiomyomas (uterine fibroids) or endometriosis
• Risk factors for thromboembolic disease (see below)
• Risk factors for estrogen-dependent cancers (eg first degree heredity for breast cancer)
• Hypertension
• Hepatopathies (eg hepatic adenoma)
• Diabetes mellitus with or without vascular involvement
• Cholelithiasis
• Migraine or headache (severe)
• Systemic lupus erythematosus
• History of endometrial hyperplasia (see below)
• Epilepsy
• Bronchial asthma
• Otosclerosis
Situations that require "immediate suspension of treatment:
Treatment must be suspended immediately if the existence of a contraindication is highlighted and in the following cases:
• Jaundice or deterioration of liver function
• Significant increase in blood pressure
• Onset of migraine-type headache
• Pregnancy
Endometrial hyperplasia and carcinoma
The risk of endometrial hyperplasia and carcinoma increases when estrogen is given alone for prolonged periods in women with an intact uterus. The observed increase in the risk of endometrial cancer among estrogen-only users is 2-12 times higher than that of non-users, depending on the duration of treatment and the dose of estrogen (see section 4.8). After discontinuation of the treatment the risk may remain high for at least 10 years.
The addition of a progestogen, such as didrogesterone, given for at least 12 days of each monthly 28-day cycle, or continuous combined estrogen-progestogen therapy in non-hysterectomised women may prevent the excess risk associated with estrogen-only HRT.
Breast cancer
In women taking combined estrogen-progestogen, and possibly estrogen-only HRT, the overall evidence suggests an increased risk of breast cancer that is dependent on the duration of taking HRT.
Combined estrogen-progestogen therapy: a randomized, placebo-controlled trial, Women "s Health Initiative study (WHI), and epidemiological studies, agree to report an increased risk of diagnosis in women taking combined estrogen-progestagen for HRT breast cancer which becomes evident after about 3 years.
The excess risk appears within a few years from the start of treatment, but returns to its initial value within a few years (at most 5) after discontinuation of treatment.
HRT, and in particular estrogen-progestogen combination therapy, increases mammographic density which may adversely affect the radiological diagnosis of breast cancer.
Ovarian cancer
Ovarian cancer is much rarer than breast cancer. Long-term use (at least 5-10 years) of estrogen-only HRT has been associated with a slightly increased risk of ovarian cancer (see Some studies, including the WHI, suggest that long-term use of combined HRT may result in a similar or slightly reduced risk (see section 4.8).
Venous thromboembolism
HRT is associated with a 1.3 - 3-fold increased risk of developing venous thromboembolism (VTE), e.g. deep vein thrombosis or pulmonary embolism.
The chance of this occurring is higher in the first year of HRT than thereafter (see section 4.8).
Patients known to have thrombophilia have an increased risk of VTE. HRT may further increase this risk. The use of HRT in these patients is therefore contraindicated.
Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index> 30 kg / m2), pregnancy / post period. childbirth, systemic lupus erythematosus (SLE) and cancer. There is no consensus on the possible role of varicose veins in VTE.
As in all post-operative patients, scrupulous attention should be given to prophylactic measures to prevent post-surgical VTE. If prolonged immobilization is planned after elective surgery, temporary suspension of the HRT for a period of 4-6 weeks before surgery. Treatment can only be resumed after complete mobilization of the patient.
For women without a personal history of VTE but with a first degree relative with a history of thrombosis at a young age, screening may be proposed, after careful evaluation of its limitations (only a part of the thrombophilic defects are identified in screening). HRT is contraindicated if a thrombophilic defect has been identified which segregates with thrombosis in family members or if the defect is 'severe' (eg antithrombin, protein S or protein C deficiency or a combination of defects).
Women already on chronic anticoagulant treatment require a "careful benefit / risk assessment of" HRT use.
If VTE occurs after initiation of therapy, the drug should be discontinued. Patients should be advised to contact their physician immediately if they experience potential symptoms of thromboembolism (eg aching leg edema, sudden chest pain, dyspnoea ).
Coronary artery disease (CAD)
There is no evidence from randomized controlled trials of protection from myocardial infarction in women with or without CAD who have taken HRT with estrogen-progestogen or estrogen alone.
Combined estrogen-progestogen therapy: The relative risk of CAD during use of estrogen-progestogen HRT is slightly increased. As the absolute baseline risk is highly age-dependent, the number of additional cases of CAD due to the use of estrogen -Progestin is very low in healthy women close to menopause, but increases in later life.
Ischemic stroke
Combined estrogen-progestogen therapy and estrogen-only therapy are associated with an up to 1.5-fold increased risk of ischemic stroke. The relative risk does not change with age or with the time since menopause.However, as the risk of stroke is highly age dependent, the additional risk of stroke in women who use HRT will increase with age (see section 4.8).
Other conditions
Estrogen can cause water retention and, therefore, patients with renal or cardiac dysfunction should be closely monitored. Patients with end-stage renal failure should be closely observed.
Women with pre-existing hypertriglyceridaemia should be followed closely during estrogen or hormone replacement therapy, as rare cases of pancreatitis following a significant increase in plasma triglycerides have been reported in women with pre-existing hypertriglyceridaemia undergoing estrogen therapy.
Estrogen increases the levels of TBG, the thyroid hormone binding globulin with consequent increase in the levels of the circulating total thyroid hormone, measured by PBI (protein bound iodine), T4 (column method or RIA) or T3 (RIA method ). T3 uptake is reduced, reflecting the increase in TBG. Free fractions of T4 and T3 are not affected. Other binding proteins such as corticoglobulin (CBG) and sex hormone binding globulin (SHBG) may be increased, and cause an increase in circulating levels of corticosteroids and sex steroids, respectively. Free or biologically active hormone fractions are unchanged. Other plasma proteins may be increased (angiotensinogen / renin substrate, alpha-I-antitrypsin, ceruloplasmin).
The use of HRT does not improve cognitive function. An increased risk of probable dementia has been observed in women who start using combined or estrogen-only HRT continuously after the age of 65.
04.5 Interactions with other medicinal products and other forms of interaction
Data in vitro indicate that didrogesterone and its major metabolite 20 alpha-didro-didrogesterone (DHD) can be metabolised by cytochrome P450 isoenzymes 3A4 and 2C19. Consequently, the metabolism of didrogesterone can be increased by the concomitant use of substances known as inducers of these isoenzymes such as anticonvulsants (eg phenobarbital, phenytoin, carbamazepine), anti-infectives (rifampicin, rifabutin, nevirapine, efavirenz) and herbal preparations containing for example St. John's wort (Hypericum perforatum), valerian root, sage or gingko biloba.
Ritonavir and nelfinavir, although known as potent inhibitors of cytochrome enzymes, by contrast, when administered together with steroid hormones, exhibit enzyme-inducing properties.
Clinically, an increased metabolism of dydrogesterone can lead to a reduction in its effect.
Education in vitro showed that didrogesterone and DHD at the concentrations reached for clinical use do not inhibit or stimulate the CYP enzymes involved in drug metabolism.
04.6 Pregnancy and lactation
Pregnancy
It is estimated that over 10 million pregnant women have been treated with dydrogesterone.
To date, there are no indications of harmful effects of didrogesterone during pregnancy.
Some progestogens have been reported in the literature to be associated with an increased risk of hypospadias. However, due to the presence of confounding factors during pregnancy, no definitive conclusions have been reached on the role of progestins in hypospadias.
Clinical studies on a limited number of women treated with dydrogesterone in the early stages of pregnancy have shown no increased risk. To date, no other epidemiological data are available.
Effects observed in embryo-fetal and postnatal developmental animal studies were in line with the pharmacological profile. Adverse effects were observed only at exposures significantly in excess of the maximum human dose, indicating limited relevance to clinical use (see section 5.3).
Dydrogesterone can be used in pregnancy if clearly indicated.
Feeding time
No data are available on the excretion of didrogesterone in breast milk. Experience with other progestogens indicates that progestogens and metabolites pass into breast milk in small quantities. It is not known if there is a risk to the newborn. However, didrogesterone should not be used during breastfeeding.
Fertility
There is no evidence that dydrogesterone used at the therapeutic dosage decreases fertility.
04.7 Effects on ability to drive and use machines
Dydrogesterone slightly affects the ability to drive or use machines.
Rarely didrogesterone may cause mild somnolence and / or dizziness, especially within the first few hours of administration. Consequently, care should be taken when driving or using machines.
04.8 Undesirable effects
The most commonly reported adverse drug reactions by patients treated with dydrogesterone in clinical trials for indications not involving concomitant use of estrogen are migraine / headache, nausea, menstrual disturbances and breast pain / tenderness.
The following undesirable effects were observed with the frequency listed below in clinical trials with dydrogesterone (n = 3483) in indications not involving concomitant use of estrogen or from spontaneous reports:
* Undesirable effect from spontaneous reporting, which has never been observed in clinical trials, to which the frequency "rare" was attributed based on the fact that the upper limit of the 95% confidence interval is not greater than 3 / x where x = 3483 (total number of subjects observed in clinical studies).
Side effects in adolescents
Based on spontaneous reports and limited data in clinical trials, an adverse reaction profile in adolescents is expected to be similar to that in adults.
Undesirable effects associated with estrogen-progestogen treatment (see also section 4.4 "Special warnings and precautions for use") and the Summary of Characteristics of the estrogen product:
- Breast cancer
- Endometrial hyperplasia and carcinoma
- Ovarian cancer
- Venous thromboembolism
- Myocardial infarction, coronary heart disease, ischemic stroke.
04.9 Overdose
There are few data available regarding overdose in humans. Dydrogesterone is well tolerated after oral administration (the maximum administered dose is 360 mg). There are no specific antidotes and treatment should be symptomatic. These indications are also applicable in patients. case of overdose in children.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Genitourinary system and sex hormones.
ATC code: G03DB01
Dydrogesterone is a selective (oral) progestin that belongs to steroids with 21 carbon atoms.
The progestin effects of didrogesterone are exerted almost exclusively on the endometrium, the vagina and the cervical mucosa.
Unlike progesterone, Dufaston at the recommended dosage does not block ovulation, nor does it depress folliculin secretion or that of the corpus luteum.
Dydrogesterone and its metabolites are not thermogenic.
The didrogesterone it has no androgenic activity (it does not present any risk of masculinization on the female fetus and no signs of virilization have ever been highlighted in the treated women), estrogenic, anabolic or corticoid.
In peri and postmenopausal women, estrogen replacement therapy leads to continuous stimulation of the endometrium. Dydrogesterone, when administered cyclically into a uterus previously stimulated by estrogen, produces a secretory transformation of the endometrium, thus protecting the endometrium from "increased risk of estrogen-induced endometrial hyperplasia and / or carcinoma. Unlike progestogens with marked androgenic activity, didrogesterone does not affect plasma concentrations of lipids and lipoproteins, maintaining the positive effects induced by estrogens on these parameters unaltered.
Teenagers
Limited clinical trial data indicate that dydrogesterone is effective in relieving the symptoms of dysmenorrhea, premenstrual syndrome, dysfunctional uterine bleeding and irregular cycles in the patient population under the age of 18 similar to that observed in the adult population.
05.2 Pharmacokinetic properties
Absorption :
After oral administration, didrogesterone is rapidly absorbed with a Tmax of between 0.5 and 2.5 hours. The absolute bioavailability of didrogesterone (an oral dose of 20 mg versus a 7.8 mg intravenous infusion) is 28%. The following table provides the pharmacokinetic parameters of didrogesterone and 20 alpha-didro-didrogesterone (DHD) following administration of a single 10 mg dose of didrogesterone:
Distribution :
After intravenous administration of dydrogesterone the volume of distribution at steady state is approximately 1,400 liters. Dydrogesterone and DHD are over 90% bound to plasma proteins.
Metabolism :
After oral administration, didrogesterone is rapidly metabolised to DHD. Peak plasma levels of the major active metabolite DHD are reached approximately 1.5 hours after administration. Plasma levels of DHD are substantially higher in comparison to the original component. The ratio of DHD to didrogesterone as AUC and Cmax is in the order of 40 and 25, respectively. The terminal mean half-lives of didrogesterone and DHD vary between 5 and 7 hours and between 14 and 7 hours, respectively. the metabolites identified is the retention of the 4,6 diene-3-one configuration of the original component and the absence of 17alpha-hydroxylation. This explains the lack of estrogenic and androgenic activity of didrogesterone.
Elimination :
After oral administration of radiolabelled dydrogesterone, on average 63% of the dose is excreted in the urine. Total plasma clearance is 6.4 l / min. Excretion is complete within 72 hours. DHD is present in the urine mainly as conjugated glucuronic acid.
Dose as a function of time
The single and multiple dose pharmacokinetic profiles are linear for oral administration of doses ranging from 2.5 to 10 mg. Comparison of single or multiple dose kinetics shows that the pharmacokinetics of didrogesterone and DHD do not change with repeated administration. Steady state is reached after 3 days of treatment.
05.3 Preclinical safety data
Non-clinical data obtained from conventional studies of single and repeated dose toxicity, genotoxicity and carcinogenic potential reveal no special hazard for humans. Reproductive toxicity studies in rats showed an "increased incidence of prominent nipples (between 11 ° and the 19th day of age) and hypospadias in male offspring, at high doses not comparable to human exposure. The actual risk of hypospadias in humans cannot be determined from animal studies due to the high species differences in metabolism between rats and humans (see also section 4.6).
Limited animal safety data suggest that didrogesterone delays parturition, an effect consistent with its progestogenic activity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Nucleus: lactose, hypromellose, corn starch, colloidal silica, magnesium stearate.
Coating film: white opadry Y-1-7000 [hypromellose, Macrogol 400, titanium dioxide (E171)].
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Blister pack consisting of aluminum foil and PVC film, carton of 14 or 42 film-coated tablets of 10 mg.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations No special instructions
07.0 MARKETING AUTHORIZATION HOLDER
Abbott Healthcare Products B.V. Weesp - Netherlands.
Sales Representative for Italy:
Abbott S.r.l., S.R. 148 Pontina km 52 snc, 04011 Campoverde di Aprilia (LT).
08.0 MARKETING AUTHORIZATION NUMBER
10 mg film-coated tablets - 14 tablets AIC n. 020008052
10 mg film-coated tablets - 42 tablets. AIC n. 020008049
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
27-08-1962
10.0 DATE OF REVISION OF THE TEXT
AIFA Resolution of 17 June 2013
