NALVEE

Posology The dosage, regimen and duration of treatment should be adjusted according to the severity of the symptoms and the clinical response.

Progesterone insufficiencies:

Dysmenorrhoea: 10 mg of dydrogesterone twice a day from day 5 to 25 of the cycle. Endometriosis: 10 mg of dydrogesterone two to three times daily from day 5 to 25 of the cycle, or continuously. Irregular menstrual cycles: 10 mg of dydrogesterone twice a day from day 11 to 25 of the cycle.

Pre-menstrual syndrome: 10 mg of dydrogesterone twice a day from day 12 to 26 of the cycle. The dosage may be increased if necessary. e. as supplement in estrogen treatment in non- hysterectomised women with symptoms due to natural onset of or surgically induced menopause: - Continuous sequential therapy: continuous use of an estrogen; sequential supplementation of 10 mg dydrogesterone during the last 14 days of each 28-day cycle - Cyclical treatment: cyclic use of an estrogen with a treatment-free period, usually 21 days on and 7 days off treatment.

For the last 12-14 days of estrogen use, 10 mg of dydrogesterone is supplemented. - Depending on the clinical response, the dosage may be adjusted to 20 mg dydrogesterone daily in the course of the treatment.

Dysfunctional uterine bleeding:

When treatment is started to arrest a bleeding episode 10 mg of dydrogesterone twice a day for five to seven days. For continuous treatment 10 mg of dydrogesterone twice a day from day 11 to day 25 of the cycle. Withdrawal bleeding occurs if the endometrium has been adequately primed with either endogenous or exogenous estrogen.

Secondary amenorrhoea: 10 mg of dydrogesterone twice a day from day 11 to 25 to produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen. There is no relevant use for dydrogesterone before menarche.

The safety and efficacy of dydrogesterone in adolescents aged 12-18 years has not been established. 1, but no recommendation on a posology can be made. Method of administration For oral use. g. always in the morning or always in the evening.

When taking 2 film-coated tablets daily, it is recommended to take one in the morning and one in the evening.

During treatment with dydrogesterone, symptoms may occur that are also common in the early phase of pregnancy, such as loss of appetite, stomach pressure, nausea, oedema and weight gain, nervous restlessness, dizziness, worsening of mood and calf cramps.

These complaints disappear when the treatment is stopped. The most commonly reported adverse reactions in patients treated with dydrogesterone in clinical trials on indications without estrogen use are migraine/headache, nausea, menstrual disorders and breast pain/tension.

The following undesirable effects have been observed in women under treatment with dydrogesterone (n=3,483) with the frequencies indicated below during clinical trials in indications without estrogen use and from spontaneous reporting: MedDRA System Organ Classes Common (>1/100 to <1/10) Uncommon (>1/1,000 to <1/100) Rare (>1/10,000 to <1/1,000) Neoplasms benign, malignant and unspecified (incl.

g. g. rash, urticaria, pruritus) Angioedema* Reproductive system and breast disorders Menstrual disorders (including metrorrhagia, menorrhagia, oligo- /amenorrhoea, dysmenorrhoea and irregular menstruation), Breast pain/tenderness Breast swelling General disorders and administration site conditions Oedema Investigations Weight gain * Adverse reactions from spontaneous reporting that were not observed in clinical trials are designated as "rare" based on the fact that the upper limit of the 95% confidence interval of the frequency estimate is no greater than 3/x, where x=3,483 (total number of subjects followed in clinical trials).

Undesirable effects in adolescents Based on spontaneous reports and limited data from clinical studies, the adverse reaction profile in adolescents is expected to be similar to that observed in adults. 4 and the information on the estrogen-containing product) - Breast cancer, endometrial hyperplasia, endometrial cancer, ovarian cancer - Venous thromboembolism - Myocardial infarction, coronary disease, ischaemic stroke Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

If dydrogesterone is prescribed for the treatment of irregular bleeding, the etiology of this bleeding should be clarified. Breakthrough bleeding and spotting may occur during the first months of treatment. If such bleeding occurs later in the course of the treatment or after the end of the treatment, the cause should be investigated and under some circumstances an endometrial biopsy should be performed to exclude endometrial malignancy.

Condition which need supervision Patients should be closely monitored if any of the following situations or conditions are present or have previously been present or have worsened during pregnancy or previous hormone treatment. It should be considered that these situations or conditions may recur or worsen during therapy with dydrogesterone and discontinuation of treatment should be considered: - Porphyria - Depression - Pathological liver function values caused by acute or chronic liver disease - Cholestatic jaundice and/or pruritus Dydrogesterone does not generally appear to affect blood pressure in normotensive women.

However, if persistent clinically significant hypertension develops during the use of dydrogesterone, it is advisable to discontinue dydrogesterone and to treat the hypertension. In higher doses, caution is advised with: - Cerebral apoplexy (also in the medical history) The following warnings and precautions apply when using dydrogesterone in combination with estrogens in hormone replacement therapy (HRT) See also the warnings and precautions in the product information of the estrogen- containing product.

HRT should only be initiated for treatment of those postmenopausal symptoms that adversely affect quality of life. In each individual case, a careful appraisal of the risks and benefits should be undertaken at least annually. HRT should only be continued as long as the benefit outweighs the risk.

There are limited data for the assessment of the risks associated with HRT in the treatment of premature menopause. Due to the low level of absolute risk in younger women, the balance of benefits and risks for these women may be more favourable than in older women.

g. g. Dubin-Johnson syndrome, Rotor syndrome) - Previous or existing liver tumours - Thrombophlebitis and thromboembolic diseases.