the package insert of the medicine Prefest. Active principles Estradiol and Norgestimato.
Prefest is indicated as hormone replacement therapy in women with uterus intact, for:
treatment of vasomotor symptoms associated with menopause;
the treatment of atrophy, vulvovaginal;
prevention of osteoporosis in post-menopausal.
When should I not use?
Prefest should not be used in women with:
Pregnancy confirmed or suspected
Malignant tumors of the breast
Neoplasia of the genital tract or other oestrogen-dependent
Genital bleeding abnormal undiagnosed
Thrombophlebitis or thromboembolic disorders or assets with a prior history
Hypersensitivity to any component of the formula of the product.
Warnings and precautions
It is recommended to obtain the medical history to complete and perform the physical examination of the patient before prescription of hormonal replacement therapy or switching from another product to prefest*. the doctor and the patient should carefully discuss the risk/benefit of long-term treatment. The clinical supervision of all the women taking combinations of estrogens and progestogens is recommended.
The following warnings are based on experience with estrogens and/or progestogens:
1. breast cancer
Some studies have reported an increased risk of breast cancer in post-menopausal women receiving hormone replacement therapy. the meta-analysis of 51 clinical studies suggests that this increased risk is comparable to that observed in women with every year of delay in menopause, the natural. This increased risk decreases after stopping use of hormone replacement therapy and is not apparent five years after cessation of treatment.
The breast cancer found in patients in use of hormone replacement therapy, or new users has a higher probability of being restricted to the breast than those of the nonusers. The concomitant use of progestin does not seem to protect against this risk. Some studies suggest that the use of progestogens may increase the risk of breast cancer in relation to therapy with estrogen alone. Therefore, careful judgement of the risk/benefit should be performed before starting treatment in the long term.
2. cancer/hyperplasia of the endometrium
It has been reported that the administration of estrogen without contrast to patients with uterus intact increases the risk of endometrial hyperplasia and carcinoma of the endometrium.
Progestogens taken with estrogens significantly reduce, but not eliminate these risks. this is the reason for the addition of the norgestimato to prefest.
The addition of intermittent norgestimato 1 mg of estradiol reduced the incidence of hyperplasia observed for < 1% with prefest.
diagnostic Measures appropriate should be taken to exclude malignancy in all cases of abnormal vaginal bleeding.
In pharmacokinetic studies with prefest, women with body weight above 80 kg showed serum peak of 17-desacetilnorgestimato 40% smaller, values of auc for 17-desacetilnorgestimato 30% smaller and the values of cmax for norgestrel 30% lower.
17-desacetilnorgestimato and norgestrel, are metabolites of the progestin norgestimato.
Although the clinical relevance of these observations is not known, the implicit risk of endometrial hyperplasia is known to be higher in overweight women. Therefore, the clinical supervision is important. diagnostic measures appropriate, including biopsy endometrial when indicated, should be taken to exclude malignancy in all cases of abnormal vaginal bleeding persistent or recurrent undiagnosed, or in women with other risk factors for endometrial hyperplasia.
3. thromboembolic disorders
Epidemiological evidence suggests that the use of hormone replacement therapy is associated with increased relative risk of development of thrombosis of deep vein or pulmonary embolism. In healthy women, the excess absolute risk of any of these conditions is about 1 in 5000 per year under hormone replacement therapy; this represents a relative risk of about 2-3. The increased risk of venous thromboembolism means that one must have caution when you use hormone replacement therapy in women at risk probably high thrombosis deep vein or pulmonary embolism. When an elective surgery that requires bed rest is planned, the hormone replacement therapy should be stopped 4 weeks before surgery. In the absence of specific data,
Prefest should be used with caution in patients immobilized.
The medication should be discontinued depending on the examination if there is sudden loss of partial or complete vision, sudden onset of proptosis or diplopia. If the examination reveals papilledema or vascular lesion of the retina, the medication should be suspended.
4. elevation of blood pressure
Increases in casual blood pressure during the replacement therapy with estrogens have been assigned to reactions idiosyncratic to estrogens. More often, blood pressure has remained the same or has fallen. A study showed that the use of estrogens in post-menopause have blood pressure higher than nonusers.
In a clinical study, extensive elevations transient systolic pressure of 40 mmhg or more compared to baseline and of the diastolic pressure of 20 mmhg or more compared to baseline were reported in less than 2% and 4% of post-menopausal women, respectively.
Two other studies showed pressures arterial slightly lower
Among users of estrogen compared with nonusers.
It has been reported that both the estrogen as progestogens affect the metabolism of carbohydrates. Patients with diabetes should be monitored appropriately and may require adjustment of the medication.
6. kidney or liver disease serious
It has been reported that post-menopausal women with end-stage renal disease had serum levels of 17â-estradiol free higher than the control subjects for both the baseline values as after the ingestion of 17â-estradiol. This indicates that the renal failure changes the pharmacokinetics of both the 17â-estradiol, the endogenous as exogenous. therefore, the doses of conventional estradiol used in individuals with normal renal function may be excessive for patients with end-stage renal disease. No study has been performed pharmacokinetic with prefest in post-menopausal women with renal insufficiency.
it is Not possible to provide recommendations for dose adjustment.
How to use?
Adults: treatment with Prefest consists in taking daily a pill. On days 1 to 3 of the treatment, the tablet contains 1.0 mg of estradiol. On days 4 to 6 the pill contains 1.0 mg of estradiol plus 90 mcg norgestimato. This dosing schedule of 3 days of estradiol isolated followed by 3 days of estradiol + norgestimato is repeated continuously throughout the treatment period.
The dosing schedule must be started on Day 1 with the first tablet from the blister pack, following the sequence printed on the packaging. The first tablet of a new pack should be taken on the first day immediately
after the last tablet of the previous packaging.
If the patient forget to take Prefest during one or more days, treatment should be restarted with the next tablet from the packaging, without skipping any pill. The patient should continue to take 1 tablet a day, in sequence, until the end of the tablets in the packaging.
Use in children
Prefest is not suitable for children.
What are the evils that can cause me?
The adverse reactions observed in clinical studies with prefest* include vaginal bleeding, “bleeding”, breast tenderness, and breast tenderness. these effects reflect the profile known from the treatment with estrogen or estrogen/progestin.
adverse Events rare reported in association with any hormone replacement therapy include: thromboembolic events, cholestasis, benign disease or malignant of the breast, carcinoma of the uterus, worsening of epilepsy, adenoma liver, and galactorrhea. if such events occur, prefest* should be discontinued immediately.
Warnings and Precautions
what should I know before using?
Tell your doctor about any medicine you are using, before the commencement, or during the treatment.
Kids: Prefest should not be used in children.
inform your doctor if you have or made some of the following boards: breast cancer, cancer/hyperplasia of the endometrium, disorders, thromboembolic, blood pressure problems, diabetes, serious illness
in the kidneys or in the liver. Your doctor will assess whether or not you can start the treatment with Prefest and whether or not you need a dose adjustment.
Prefest should not be used as a contraceptive.
Contra-indications: do Not use Prefest if you:
* you are pregnant or suspect that you are pregnant
* is allergic to any of the other components of the drug
* has malignant tumor of the breast
* has a tumor of the genital tract
* shows genital bleeding abnormal of unknown origin
* presents or has presented thrombophlebitis or problems thromboembolic.
what to do if someone use a larger amount than is recommended?
The excessive dose of Prefest may cause nausea, vomiting, breast tenderness and breakthrough bleeding. Deleterious effects serious have not been reported after acute ingestion of large doses of hormones replacement