Duphaston Special Precautions

Before initiating dydrogesterone treatment for dysfunctional uterine bleeding, an organic cause must be ruled out.
Breakthrough bleeding and spotting may occur during the first months of treatment. If breakthrough bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, if necessary by endometrial biopsy to exclude endometrial malignancy.
If any of the following disorders occurs for the first time or worsens during use, discontinuation of the treatment must be considered: Exceptionally severe headache, migraine or symptoms which might suggest cerebral ischaemia.
A notable rise in blood pressure.
Occurrence of venous thromboembolism.
In cases of habitual and threatened miscarriage, the viability of the foetus should be determined and checked during treatment to see if the pregnancy is continuing and whether the embryo is still alive.
Conditions which need monitoring: It is known that the following rare conditions can be influenced by sex hormones, and during pregnancy or during the use of sex hormones may occur or worsen: cholestatic jaundice, herpes gestationis, severe pruritus, otosclerosis and porphyria.
Patients with a history of depression should be monitored carefully. If severe depression recurs, the treatment with dydrogesterone must be stopped.
Other conditions: Patient with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The following warnings and precautions apply when using dydrogesterone in combination with oestrogens for hormone replacement therapy (HRT): See also the warnings and precautions in the product information of the oestrogen preparation.
For the treatment of postmenopausal symptoms, HRT should be initiated only if these symptoms adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and the treatment should be continued only if the benefit outweighs the risks.
Medical examination/follow-up: Before initiating or re-instituting hormone replacement therapy (HRT), a complete medical history (including family history) should be taken. Physical (including gynaecological and mammary) examinations should be guided by the history and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature suited to each individual woman. Women should be advised what changes in their breasts should be reported to their doctor (see Breast cancer as follows).
Investigations, including imaging procedures, e.g., mammography, should be carried out in accordance with the applicable screening guidelines, taking into account the medical situation of the individual woman.
Endometrial hyperplasia and carcinoma: In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma is increased with long-term use of oestrogens without the addition of progestogen. Depending on the duration and the oestrogen dose, the risk is 2 to 12 times higher than in women who do not take any oestrogen. After stopping the oestrogen treatment, the risk remains for at least 10 years. This additional risk can be prevented by combining the oestrogen therapy for at least 12 days per month/28-day cycle with a progestogen, such as dydrogesterone.
Breakthrough bleeding and spotting may occur during the first months of treatment. If breakthrough bleeding or spotting occur after taking the therapy for some time or if they continue after the treatment has ended, further investigation is then indicated. This may mean that an endometrial biopsy should be carried out so as to be able to rule out malignancy.
Breast cancer: All available data showed an increased risk of breast cancer if women take combined estrogen-progestogen or estrogen-only HRT. This risk is dependent on the duration of its use.
Combined treatment with oestrogen and progestogen: The randomized, placebo-controlled trial, (Women's Health Initiative study (WHI)), and a meta-analysis of prospective epidemiological studies are consistent in finding an increased risk of breast cancer after about 3 (1-4) years of use. Results from a large meta-analysis showed that after stopping treatment, the excess risk will decrease with time and the time needed to return to baseline depends on the duration of prior HRT use. When HRT was taken for more than 5 years, the risk may persist for 10 years or more. HRT treatment, especially combined oestrogen and progestogen treatment, increases the density of the mammographic images which may adversely affect the radiological detection of breast cancer.
Ovarian cancer: Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only or combined oestrogen-progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping. Some other studies including the WHI study, suggest that the use of combined HRTs may be associated with a similar, or slightly smaller, risk.
Venous thromboembolism: HRT is associated with a 1.3 to 3 times greater risk of developing venous thromboembolism (VTE), i.e., deep vein thrombosis or pulmonary embolism. The possibility of this occurring is greater in the first year of HRT than later.
Patients with known thrombophilia have an increased risk of VTE and HRT may add to this risk. HRT is therefore also contraindicated in these patients.
Generally recognized risk factors for VTE include the use of oestrogens, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m²), pregnancy/postpartum period, systemic lupus erythematosus (SLE), and cancer. There is no consensus about the possible role of varicose veins in VTE.
In all postoperative patients, measures need to be considered to prevent VTE following surgery. If prolonged immobilization is to follow elective surgery, temporarily stopping HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is completely mobilized.
In women with no personal history of VTE but with a first degree relative with a history of thrombosis at young age, screening may be offered after careful counseling regarding its limitations (only a proportion of thrombophilic defects are identified by screening). If a thrombopihilic defect is identified which has led to thrombosis in family members or if the defect is severe (e.g. antithrombin, protein S, or protein C deficiencies or a combination of defects) HRT is contraindicated.
Women already on anticoagulant treatment should carefully weigh the benefits and risks of using HRT.
If VTE develops after initiating therapy, the drug should be discontinued. Patient should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. pain swelling of a leg, sudden pain in the chest, dyspnea).
Coronary artery disease (CAD): There is no evidence from randomized controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined oestrogen-progestogen or oestrogen-only HRT.
Combined oestrogen-progestogen therapy: The relative risk of CAD during use of combined oestrogen-progestogen HRT is slightly increased. As the baseline absolute risk of CAD is strongly dependent on age, the number of extra cases of CAD due to oestrogen-progestogen use is very low in women close to menopause, but will rise with more advanced age.
Ischaemic stroke: Use of combined HRT or HRT using oestrogen alone is associated with a 1 to 1.5 times greater risk of ischaemic stroke. The relative risk does not change with age or time since menopause. However, as the baseline risk of stroke is strongly age-dependent, the absolute risk of stroke will increase with age.
Excipients: This medicinal product contains Lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Dydrogesterone has minor influence on the ability to drive and use machines.
Infrequently, dydrogesterone may cause mild somnolence and/or dizziness, especially within the first few hours after intake. Therefore, care should be taken when driving or using machines.