Dienogest + Estradiol Valerate

This is indicated for-

• Relief of post-menopausal symptoms associated with decrease of estrogen hormones including hot flushes and vaginal dryness
• Women who desire the complete stoppage of menstrual bleeding after its intermittent recurrence due to impending menopause
• Women who displayed undue obstruction of normal daily activities due to menopausal symptoms.

This is categorized as antiandrogenic gestagen effective in reducing and alleviating the anxiety of menopausal symptoms. This is a Hormone Replacement Therapy (HRT). It contains two types of female hormones, an oestrogen and a progestogen. This is used in postmenopausal women with at least 12 months since their last natural period and who still have their uterus.

The two active components of this, estradiol valerate and dienogest are combined to effectively reduce the red flushes, vaginal dryness and irritation commonly experienced by women after menopause. Oestrogen served numerous body processes, one of which is by controlling the secretion of hormones secreted by the pituitary glands (such as the ganadotropins, luteinizing and follicle-stimulating hormones) that are elevated during post menopausal. Oestrogen works by lowering the level of these hormones that usually occurs on women after menopause. Dienogest on the other hand, is a form of progestin that works as a binding progesterone receptor. It transforms the secretory function of the endometrium and protects against endometrial proliferation. The combination of these 2 substances effectively prevents the recurrence of menstrual bleeding which usually occurs with sequential Hormone Replacement Therapy.

One tablet should be taken daily at the same time blister packet. blister packet. Each blister pack contains tablets for 28 days of treatment. This is for oral use only. The tablets are to be swallowed whole with some liquid. Treatment is continuous, which means that the next pack follows immediately without a break. The tablets should preferably be taken at the same time every day. In case a tablet is forgotten it should be taken as soon as possible. If more than 24 hours have elapsed no extra tablet needs to be taken. If several tablets are forgotten, bleeding may occur.

Some medicines may interfere with the effect of this tablet. This might lead to irregular bleeding. This applies to the following medicines:

• Medicines for epilepsy (such as phenobarbital, phenytoin, carbamazepine)
• Medicines for tuberculosis (such as rifampicin and rifabutin)
• Medicines for HIV infection (e.g. nevirapine, efavirenz, ritonavir and nelfinavir)
• Herbal remedies containing St. John’s wort (Hypericum perforatum).

• Known past or suspected breast cancer
• Known or suspected estrogen-dependent malignant tumors (e.g. endometrial cancer)
• Undiagnosed genital bleeding
• Untreated endometrial hyperplasia
• Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
• Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• Porphyria
• Hypersensitivity to the active substances or to any of the ingredients

The following diseases are reported more often in women using HRT compared to women not using HRT: Breast cancer, Abnormal growth or cancer of the lining of the womb (endometrial hyperplasia or cancer), Ovarian cancer, Blood clots in the veins of the legs or lungs (venous thromboembolism), Heart disease, Stroke, Probable memory loss if hrt is started over the age of 65

Most frequent side effects: unexpected menstruation-like bleeding, breast tenderness, breast pain Unexpected menstruation-like bleeding occurs during the first few months of treatment with this medicine. Usually temporary and normally disappears with continued treatment. If it does not, contact your doctor.

Common side effects (between 1 and 10 in every 100 patients are likely to get these):

• headache, migraine, dizziness, tiredness, anxiety, depressive mood
• high blood pressure, worsening of high blood pressure
• feeling sick, abdominal pain, diarrhoea, increase in gamma gt (an enzyme)
• thickening of the lining of the womb, inflammation of the genitals, swollen breasts
• hot flushes
• changes in body weight, thrush

Uncommon side effects (between 1 and 10 in every 1000 patients are likely to get these):

• sleeplessness, nervousness
• inflammation of the veins, venous blood clot (leg pain), painful veins
• constipation, swollen tummy (bloating), inflammation of the stomachincreased sweating, hair loss, a variety of skin conditions such as exanthema, eczema and acne-like
• Dermatitis acnechanges in vaginal secretions, lumpy breasts (fibrocystic disease)
• allergic reactions
• fluid retention in the legs, altered blood fats, increase in blood sugar, change in sex drive, muscle
• Cramps, anaemia

Rare side effects (between 1 and 10 in every 10,000 patients are likely to get these): Depression, visual disorders, palpitations, indigestion, disturbances in liver enzymes, increase in the size of fibroids, increased appetite.

This is for use in post-menopausal women only. If you become pregnant, stop taking and contact your doctor. If you are lactating mother, stop taking this tablet and contact your doctor.

If you have ever had any of the following problems, before you start the treatment, as these may return or become worse during treatment with this tablet. If so, you should see your doctor more often for check-ups:

Uterine Fibroids, Endometriosis, Endometrial hyperplasia, Increased risk of developing blood clots, Risk factors for estrogen-dependent tumours, e.g. 1st-degree heredity for breast cancer, High blood pressure, A liver disorder, such as a benign liver tumour, Diabetes, Gallstones, Migraine or severe headaches, Systemic Lupus, Erythematosus, Epilepsy, Asthma, Otosclerosis, A very high level of fat in your blood (triglycerides), Fluid retention due to cardiac or kidney problems, Hereditary angioedema, products containing oestrogens may cause or worsen the symptoms.

You should see your doctor immediately if you experience symptoms of angioedema such as: Swollen face, tongue and/or throat and/or difficulty swallowing, or hives together with, Difficulty breathing.

Stop taking this tablet and see a doctor immediately: Jaundice or deterioration in liver function, Significant increase in blood pressure, New onset of migraine-type headache, Pregnancy. If you notice signs of a blood clot, such as, Painful swelling and redness of the legs, Sudden chest pain, or difficulty breathing.

HRT and cancer: Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer). Taking oestrogen-only HRT will increase the risk of excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer) The progestogen in this tablet protects you from this extra risk.

Irregular bleeding: You may have irregular bleeding or drops of blood (spotting) during the first 3-6 months of taking this tablet. However, if the irregular bleeding: carries on for more than the first 6 months.

Breast cancer: Evidence suggests that taking combined oestrogen-progestogen and possibly also oestrogen-only HRT increases the risk of breast cancer. This extra risk depends on how long you take HRT. The additional risk becomes clear within a few years. However, it returns to normal within a few years (at most 5) after stopping treatment.

Blood clots in a vein (thrombosis): The risk of blood clots in the veins is about 1.3 to 3-times higher in HRT users than in non-users, especially during the first year of taking it. Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, breathlessness, fainting or even death. Inform your doctor if any of these situations applies to you:

• you are unable to walk for a long time because of major surgery, injury or illness
• you are seriously overweight (bmi >30 kg/m²)
• you have any blood clotting problem that needs long-term treatment with a medicine used to prevent blood clots
• if any of your close relatives has ever had a blood clot in the leg, lung or an other organ
• you have systemic lupus erythematosus (sle)
• you have cancer

Heart disease (heart attack): There is no evidence that HRT will prevent a heart attack. Women over the age of 60 years who use oestrogen-progestogen HRT are slightly more likely to develop heart disease than those not taking any HRT.

Stroke: The risk of getting stroke is about 1.5 times higher in HRT users than in non-users. The number of extra cases of stroke due to use of HRT will increase with age.

Acute toxicity studies indicated that, even in the case of inadvertent intake of a multiple of the therapeutic dose, no acute toxicity risk is to be expected. Overdose may cause nausea and vomiting, and withdrawal bleeding may occur in some women. There is no specific antidote.

Drugs for menopausal symptoms: Hormone replacement therapy, Female Sex hormones

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.