Dosing Considerations VISANNE tablets are intended for continuous administration in women for the management of pelvic pain associated with endometriosis. Drug administration can be started on any day of the menstrual cycle. Special Populations Pediatrics (< 18 years of age) The use of VISANNE in adolescent females (12 to < 18 years) over a 12 month period of time is associated with a decrease in bone mineral density (BMD).
After cessation of treatment, BMD increases towards pre-treatment levels. Plateauing or loss of BMD is of particular concern during adolescence and early adulthood, as this is critical period of bone accretion. Therefore, the treating physician should weigh the benefits of VISANNE against the possible risks of use in each individual adolescent patient, also taking into account the presence of significant risk factors for osteoporosis.
BMD monitoring should be considered in adolescent females using VISANNE, as clinically appropriate. Recommended Dose and Dosage Adjustment The dosage of VISANNE is 1 tablet taken orally every day without a break, preferably at the same time each day, with some liquid as needed.
Tablets must be taken continuously regardless of any vaginal bleeding. When a pack is finished, the next one should be started the next day. VISANNE may be taken with or without food. Missed Dose In the event of a missed tablet, a patient should take 1 tablet only as soon as possible and then continue to take the next tablet at her usual time the next day.
The efficacy of VISANNE may be reduced in the event of missed tablets, vomiting and/or diarrhea (if occurring within 3 to 4 hours after the tablet is taken). A tablet not absorbed due to vomiting or diarrhea should likewise be replaced by 1 tablet.
OVERDOSAGE A clinical study has shown that 20 to 30 mg dienogest per day (10 to 15 times the recommended dose of VISANNE) over 24 weeks of use in women was generally well tolerated. (9) There is no specific antidote to a VISANNE overdose and further treatment should be symptomatic, based on the pharmacological action of dienogest (see TOXICOLOGY, Acute Toxicity).
For management of a suspected overdose please contact your regional Poison Control Centre. VISANNE Product Monograph Page 16 of 40 ACTION AND CLINICAL PHARMACOLOGY Mechanism of Action Dienogest is a novel nortestosterone derivative with no androgenic but rather an antiandrogenic activity of approximately one third that of cyproterone acetate.
(10) Dienogest binds to the progesterone receptor of the human uterus with only 10% of the relative affinity of progesterone. Despite its low affinity to the progesterone receptor, dienogest has a strong progestogenic effect in vivo.
Dienogest has no significant androgenic, mineralocorticoid, or glucocorticoid activity in vivo. Pharmacodynamics Dienogest reduces the endogenous production of estradiol and thereby suppresses the trophic effects of estradiol on both the eutopic and ectopic endometrium.
When given continuously, dienogest leads to a hyperprogestogenic and moderately hypoestrogenic endocrine environment causing initial decidualization of endometrial tissue. (11) Additional direct antiproliferative, immunologic and antiangiogenic effects seem to contribute to the inhibitory action of dienogest on cell proliferation (11-13) and to the reduction of pelvic pain associated with endometriosis.
Bone Mineral Density The pharmacologic action of dienogest results in suppression of the hypothalamic-pituitary- ovarian axis, causing a moderate suppression of serum estrogen concentrations. This may lead to a decrease in bone mineral density, including during adolescence, a critical period of bone accretion.
The potential risk for a future fracture, however, is not known (see WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, and WARNINGS AND PRECAUTIONS, Special Populations). Ovarian Function In a study in 20 healthy women, a daily dose of 2 mg dienogest has been shown to induce an anovulatory state after 1 month of treatment.
VISANNE has not been tested for contraceptive efficacy. VISANNE is not intended for use as a contraceptive. If contraception is required, a nonhormonal method should be used (see WARNINGS AND PRECAUTIONS, General). Endogenous estrogen levels are only moderately suppressed during treatment with VISANNE.
Based on available data, the menstrual cycle returns to pretreatment characteristics within 2 months after cessation of treatment with VISANNE. Hypothalamo-Hypophyseal Function Administered exogenously and continuously, progestins reduce the frequency and increase the amplitude of pulsatile GnRH release, which results in a reduction of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion.
VISANNE does not increase the incidence or intensity of hot flushes. VISANNE Product Monograph Page 17 of 40 Pharmacokinetics Pharmacokinetics of dienogest are not influenced by sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG) levels.
24-fold reaching steady-state conditions after 4 days of treatment. The pharmacokinetics of dienogest after repeated administration of VISANNE can be predicted from single-dose pharmacokinetics. The pharmacokinetics of dienogest are dose-proportional and linear within the dose range of 1 to 8 mg.
There is minimal accumulation with repeated administration (accumulation ratio 1:24) and neither the time to maximum concentration nor the terminal half-life are altered compared to single-dose administration. Absorption Orally administered dienogest is rapidly and almost completely absorbed.
5 hours after single ingestion of 2 mg. Bioavailability is about 91%. The pharmacokinetics of dienogest are dose-proportional within the dose range of 1 to 8 mg. Distribution Dienogest is bound to serum albumin and does not bind to sex hormone binding globulin (SHBG) or corticoid binding […]