Estalis Continuous
Estalis Continuous Uses, Dosage, Side Effects, Food Interaction and all others data.
Estradiol is a naturally occurring oestrogen. Oestrogens are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. They modulate the pituitary secretion of gonadotrophins, LH and FSH through a negative feedback system.
Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia).
Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland.
A note on hyper-coagulable state, cardiovascular health, and blood pressure
| Trade Name | Estalis Continuous |
| Generic | estradiol + norethisterone acetate |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Australia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Treatment of moderate to severe vasomotor symptoms associated with the menopause.
Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease.
Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).
Prevention of osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.
Norethisterone is indicated in: Metropathia hemorrhagic (dysfunctional uterine bleeding), Premenstrual syndrome, Postponement of menstruation, Endometriosis & Menorrhagia.Estalis Continuous is also used to associated treatment for these conditions: Atrophic Vaginitis, Breast Cancer, Breast engorgement caused by Postpartum state, Hypogonadism female, Kraurosis Vulvae, Metastatic Breast Cancer, Osteoporosis, Postmenopausal Osteoporosis, Premature Ovarian Failure (POF), Prostate Cancer, Urogenital atrophy, Vasomotor Symptoms Associated With Menopause, Vulvovaginal Atrophy, Advanced androgen dependent Prostate cancer, Female castration, Hypoestrogenism, Contraception, Hormone Replacement Therapy, Palliation
How Estalis Continuous works
Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes 70 to 500 mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women.
Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems.
Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state.
Dosage
Estalis Continuous dosage
Oral:
- Prostate cancer: 10 mg 3 times/day for at least 3 month.
- Menopausal vasomotor symptoms: 1-2 mg/day on a cyclical or continuous regimen
- Prevention of postmenopausal osteoporosis: 0.5 mg/day in cyclical regimen.
- Hypogonadism: 1-2 mg/day in a cyclic regimen.
Vaginal:
- Vulvular and vag atrophy: Insert 2-4 g/day for 2 wk. Maintenance: 1 g 1-3 times/wk.
- Postmenopausal vag atrophy; Urogenital symptoms: Insert a ring and keep in place for 90 days.
- Atrophic vaginitis: Insert 1 tab once daily for 2 wk. Maintenance: 1 tab twice wkly. Attempt to discontinue or taper medication at 3-6 monthly intervals.
Side Effects
GI disturbances, genitourinary changes, haematologic disorders, CV and CNS effects, endocrine and metabolic disorders, cholestatic jaundice, local skin reactions, chorea, contact lens intolerance, steeping of corneal curvature, pulmonary thromboembolism, carbohydrate intolerance.
Side-effects are more common during the first months after start of intake of Norethisterone, and subside with a duration of treatment. The side-effects are mentioned below: Eye disorders- Visual disturbance GI disorders- Nausea General disorders and administration site- conditions headache, edema Nervous system disorders- Migraine, Respiratory, thoracic and mediastinal disorders- Dyspnoea, Skin and subcutaneous tissue disorders- Hypersensitivity (eg. Rash, urticaria).Toxicity
The NOAEL (no-observed-adverse-effect-level) oral toxicity of estradiol after 90 day in rats was 0.003 mg/kg/day for blood, female reproductive, and male reproductive, endocrine, and liver toxicity. Oral TDLO of ethinyl estradiol is 21 mg/kg/21D intermittent, woman) with an oral LD50 of 960 mg/kg in the rat.
There is limited information in the literature regarding estrogen overdose. Estradiol overdose likely leads to the occurrence of estrogen-associated adverse effects, including nausea, vomiting, abdominal pain, breast tenderness, venous thrombosis, and vaginal bleeding. It is generally recommend to discontinue estradiol treatment and offer supportive care in the case of an overdose.
Precaution
Conditions exacerbated by fluid retention; hypercalcaemia, cerebrovascular diorders, coronary artery disease, gall bladder diseases; lipid effects; familial defects of lipoprotein metabolism. May increase BP, risk of venous thromboembolism, breast cancer, benign hepatic adenoma, endometrial cancer and size of preexisting uterine leiomyomata. Dosage should be reduced in hepatic impairment. Lactation. Child.
There is a general opinion, based on statistical evidence that users of combined oral contraceptives experience, more often than non-users, venous thromboembolism, arterial thrombosis, including cerebral and myocardial infarction and subarachnoid haemorrhage. Full recovery from such disorders does not always occur, and it should be realized that in a few cases they are fatal. Although Norethisterone does not contain oestrogen, one should keep the possibility of an increased thromboembolic risk in mind, particularly where there is a history of thromboembolic disease or in the presence of severe diabetes with vascular changes or sickle-cell anaemia.In rare cases benign, and in even rarer cases, malignant liver tumours leading in isolated cases to life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal substances such as the one contained in Norethisterone. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be included in the differential diagnosis and, if necessary, the preparation should be withdrawn.Norethisterone can influence carbohydrate metabolism. Parameters of carbohydrate metabolism should be examined carefully in all diabetics before and regularly during treatment.Reasons for stopping Norethisterone immediately- Occurrence for the first time of migrainous headaches or more frequent occurrence of unusually severe headaches Sudden perceptual disorders (e.g. disturbances of vision or hearing) First signs of thrombophlebitis or thromboembolic symptoms, feeling of pain and tightness in the chest Pending operations (six weeks beforehand), immobilisation (e.g. after accidents) Onset of jaundice, hepatitis, general pruritus Significant rise in blood pressure Pregnancy.Interaction
CYP1A2 and CYP3A4 inducers e.g. aminoglutethimide, carbamazepine, phenobarbital, and rifampin may decrease the effects of estradiol. May enhance the effects of hydrocortisone and prednisolone when used together.
Not known.Volume of Distribution
Estrogens administered exogenously distribute in a similar fashion to endogenous estrogens. They can be found throughout the body, especially in the sex hormone target organs, such as the breast, ovaries and uterus.
Elimination Route
The absorption of several formulations of estradiol is described below:
Oral tablets and injections
First-pass metabolism in the gastrointestinal tract rapidly breaks down estradiol tablets before entering the systemic circulation. The bioavailability of oral estrogens is said to be 2-10% due to significant first-pass effects. The esterification of estradiol improves the administration (such as with estradiol valerate) or to sustain release from intramuscular depot injections (including estradiol cypionate) via higher lipophilicity. After absorption, the esters are cleaved, which leads to the release of endogenous estradiol, or 17β-estradiol.
Transdermal preparations
The transdermal preparations slowly release estradiol through intact skin, which sustains circulating levels of estradiol during a 1 week period of time. Notably, the bioavailability of estradiol after transdermal administration is about 20 times higher than after oral administration. Transdermal estradiol avoids first pass metabolism effects that reduce bioavailability. Administration via the buttock leads to a Cmax of about 174 pg/mL compared to 147 pg/mL via the abdomen.
Spray preparations
After daily administration, the spray formulations of estradiol reach steady state within 7-8 days. After 3 sprays daily, Cmax is about 54 pg/mL with a Tmax of 20 hours. AUC is about 471 pg•hr/mL.
Vaginal ring and cream preparations
Estradiol is efficiently absorbed through the mucous membranes of the vagina. The vaginal administration of estrogens evades first-pass metabolism. Tmax after vaginal ring delivery ranges from 0.5 to 1 hour. Cmax is about 63 pg/mL. The vaginal cream preparation has a Cmax of estradiol (a component of Premarin vaginal estrogen conjugate cream) was a Cmax of 12.8 ± 16.6 pg/mL, Tmax of 8.5 ± 6.2 hours, with an AUC of 231 ± 285 pg•hr/mL.
Half Life
The terminal half-lives for various estrogen products post oral or intravenous administration has been reported to range from 1-12 hours. One pharmacokinetic study of oral estradiol valerate administration in postmenopausal women revealed a terminal elimination half-life of 16.9 ± 6.0 h. A pharmacokinetic study of intravenous estradiol administration in postmenopausal women showed an elimination half-life of 27.45 ± 5.65 minutes. The half-life of estradiol appears to vary by route of administration.
Clearance
In one pharmacokinetic study, the clearance of orally administered micronized estradiol in postmenopausal women was 29.9±15.5 mL/min/kg. Another study revealed a clearance of intravenously administered estradiol was 1.3 mL/min/kg.
Elimination Route
Estradiol is excreted in the urine with both glucuronide and sulfate conjugates.
Pregnancy & Breastfeeding use
Pregnancy Category X. Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
The administration of Norethisterone during pregnancy is contraindicated. Norethisterone should not be used during lactation.Contraindication
Hypersensitivity; undiagnosed vag bleeding; thrombophloebitis or thromboembolic disorders; breast carcinoma except in selected patients being treated for metastatic disease; oestrogen-dependent tumor; porphyria; pregnancy.
Pregnancy Severe disturbances of liver function Dubin-Johnson syndrome Rotor syndrome Previous or existing liver tumours History during pregnancy of idiopathic jaundice, severe pruritus or herpes gestationis Current thromboembolic processes Hypersensitivity to the active substances or to any of the excipientsAcute Overdose
There have been no reports from overdosage and treatment is generally unnecessary. There are no special antidotes and treatment should be symptomatic.Storage Condition
Store at room temperature.
Store below 30°C in a cool & dry place. Keep out of reach of children.Innovators Monograph
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