Product Overview
[Drug name]
Generic name: Estriol cream
Trade name: Ouweiting
Chinese pinyin: Cisanchunrugao
[Ingredients]
The main ingredient of this product is estriol.
[Indications]
Urogenital tract atrophy symptoms caused by estrogen deficiency; prevention of recurrent vaginitis and lower urethral infection; frequent urination, dysuria and mild urinary incontinence. It can also be used for postmenopausal women before and after vaginal surgery, and suspected atrophic cervical smear auxiliary diagnosis.
[Usage and Dosage]
Atrophy of the lower urethra
Use once a day in the first week, and then gradually reduce to a maintenance dose (for example, twice a week) according to the relief of symptoms. For urinary incontinence, some women may need a higher maintenance dose.
-Postmenopausal women before and after vaginal surgery.
Once a day for two weeks before surgery and twice a week for two weeks after surgery.
-Suspected atrophic cervical smear auxiliary diagnosis
Once every two days in a week before the next smear test.
Estriol cream should be delivered to the vagina through a dispenser before going to bed at night. Each time (the filling scale is marked on the applicator), 0.5g of Ovetin cream is used, which contains 0.5mg of estriol.
Patient use method
1. Use this vaginal cream before going to bed at night.
2. Unscrew the cap of the cream tube, turn the tube mouth upward, and poke the tube mouth with a sharp object.
3. Screw the applicator opening onto the cream tube mouth.
4. Squeeze the cream tube to squeeze the milk tube into the applicator until the pusher of the applicator stops.
5. Unscrew the applicator opening from the cream tube mouth and cover the cream tube mouth with a cap.
6. The recipient lies flat, inserts the end of the applicator into the vaginal bottom, and slowly pushes the pusher to inject all the medicine into the vagina.
After use, pull the pusher out of the applicator tube and wash both parts with warm soapy water. Do not use detergent. Then rinse with clean water.
Please do not put the applicator in hot or boiling water.
If you forget to take a medication, you should take it immediately if it is not on the next medication day. Otherwise, you should skip the forgotten medication and continue to take it as usual. You should never take a medication twice on the same day.
[Adverse Reactions]
Based on the literature and safety monitoring data, the following adverse reactions have been reported: These adverse reactions are usually transient, but may also indicate excessive dosage. Other adverse reactions reported to be associated with estrogen-progestin therapy. Due to the lack of relevant information, it is unclear whether Ovetin is different from other similar drugs in this regard. middot; Benign and malignant estrogen-dependent tumors, such as endometrial cancer and breast cancer. For details, see [Contraindications] and [Precautions]. middot; The incidence of venous thromboembolism (i.e., deep vein thrombosis of the lower limbs or pelvis and pulmonary embolism) is higher in HRT users than in non-users. Due to the lack of relevant information, it is unclear whether Ovetin is different from other similar drugs in this regard. For details, see [Contraindications] and [Precautions]. middot; Myocardial infarction and stroke middot; Gallbladder disease middot; Skin and subcutaneous tissue abnormalities: chloasma, erythema multiforme, erythema nodosum, and vascular purpura. middot; Suspected dementia (see [Precautions]) [u] Breast cancer [/u] According to data from a large number of epidemiological studies and a randomized placebo-controlled trial - Women's Health Initiative (WHI), the overall risk of breast cancer increases with the duration of treatment in current or recent users of HRT. Regarding estrogen-only HRT, the relative risk (RR) estimate obtained by reanalyzing the data of 51 epidemiological studies (more than 80% of which were estrogen-only HRT) was similar to the RR estimate from the epidemiological Million Women Study (MWS), which were 1.35 (95% CI 1.21-1.49) and 1.30 (95% CI 1.21-1.40), respectively. Regarding estrogen-progestin combined HRT, some epidemiological studies reported that its overall risk of breast cancer is higher than that of estrogen-only HRT. The MWS report pointed out that compared with women who have never used HRT, users of various types of estrogen-progestin combined with HRT have a higher risk of breast cancer (RR = 2.00, 95% CI: 1.88-2.12) than women who use estrogen alone (RR = 1.30, 95% CI: 1.21-1.40) or tibolone (RR = 1.45, 95% CI: 1.25-1.68). The WHI study report pointed out that compared with placebo, the relative risk estimate of all users who received estrogen-progestin combined with HRT (CEE + MPA) after 5.6 years of treatment was 1.24 (95% CI 1.01-1.54). The absolute risk values calculated in the MWS and WHI trials are shown as follows: Based on the known average breast cancer incidence in developed countries, the MWS estimates: middot; For those who do not use HRT, the proportion of women aged 50 to 64 years diagnosed with breast cancer is expected to be 32/1000. middot;For every 1,000 current or recent users of HRT, the estimated number of additional breast cancer cases diagnosed in women aged 50 to 64 years is: - For estrogen replacement therapy alone * 0 to 3 additional cases for 5 years (best estimate 1.5 cases). * 3 to 7 additional cases for 10 years (best estimate 5 cases). - For users of combined estrogen-progestin HRT * 5 to 7 additional cases for 5 years (best estimate 6 cases). * 18 to 20 additional cases for 10 years (best estimate 19 cases). After 5.6 years of follow-up of women aged 50 to 79 years, the WHI trial estimated that there would be 8 additional cases of invasive breast cancer per 10,000 woman-years due to the use of combined estrogen-progestin HRT (CEEMPA). Based on calculations from this trial data, it is estimated that: middot;For every 1,000 women in the placebo group, 16 additional cases of invasive breast cancer will be diagnosed within 5 years. middot;For every 1,000 women using combined estrogen-progestin HRT (CEE + MPA), the number of additional cases will be - 0 to 9 cases for 5 years (the best estimate is 4 cases). Regardless of the age at which HRT is started (between 45 and 65 years old), the number of additional breast cancer cases in women using HRT is similar (see [Precautions]).
[Contraindications]
Known, suspected or previous breast cancer. Known or suspected estrogen-dependent malignancies (such as endometrial cancer). Undiagnosed vaginal bleeding. Untreated endometrial hyperplasia. Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism). Active or recent arterial thromboembolic disease (such as angina pectoris, myocardial infarction). Acute liver disease, or history of liver disease with liver function tests that cannot return to normal. Known allergy to the active ingredient or any excipients of the drug. Porphyria.
【Precautions】
For the treatment of postmenopausal symptoms, hormone replacement therapy (HRT) should be started only when these symptoms affect the quality of life. A careful risk-benefit assessment should be performed at least once a year for each patient receiving treatment, and HRT should be continued only when the benefits outweigh the risks. [u]Medical Examination/Follow-up[/u]middot;Before starting HRT for the first time or restarting it, a complete personal and family history should be investigated, and a physical examination (including pelvic and breasts) should be performed based on this, as well as contraindications and precautions for use. During treatment, regular physical examinations are recommended according to individual differences. Women should be advised to report breast changes to their doctors or caregivers (see "Breast Cancer" below). Examinations, including mammography, should be performed in accordance with currently accepted screening procedures and combined with individual clinical needs. [u]Conditions to be monitored[/u]middot;If any of the following conditions are currently present or have occurred previously, and/or have been aggravated during pregnancy or previous hormone therapy, the patient should be closely monitored. The possibility of recurrence or aggravation of these conditions should be taken into account during treatment with Ovetin, in particular: - leiomyoma (uterine fibroids) or endometriosis - history of or risk factors for thromboembolic diseases (see below) - risk factors for estrogen-dependent tumors, such as first-degree hereditary breast cancer - hypertension - liver disease (e.g. hepatic adenoma) - diabetes mellitus with or without vascular disease - cholelithiasis - migraine or (severe) headaches - systemic lupus erythematosus - history of endometrial hyperplasia (see below) - epilepsy - asthma - otosclerosis [u]Reasons for immediate discontinuation of treatment [/u] [u] Treatment should be discontinued if contraindications are detected and in the following circumstances: [/u] middot; jaundice or worsening of liver function middot; marked increase in blood pressure middot; new onset of migraine headache middot; pregnancy [u] Endometrial hyperplasia [/u] To prevent irritation of the endometrium, the daily dose should not exceed the single dose (0.5 mg estriol) and this maximum dose should not be used continuously for more than several weeks. An epidemiological study showed that long-term use of low-dose oral estriol, rather than vaginal estriol, may increase the risk of endometrial cancer. This risk increases with the duration of treatment and disappears within 1 year after stopping treatment. The increased risk mainly involves low-grade invasive and well-differentiated tumors. Vaginal bleeding during treatment must be investigated, and patients should be informed to contact their doctor immediately if vaginal bleeding occurs. [u]Breast Cancer[/u]middot;HRT may increase mammographic density. This may complicate the radiological detection of breast cancer. Clinical studies have shown that subjects treated with estriol are less likely to have an increase in mammographic density than those treated with other estrogen treatments. middot;A randomized placebo-controlled trial, the Women's Health Initiative (WHI), and epidemiological studies including the Million Women Study (MWS) reported an increased risk of breast cancer in women who received HRT for several years with estrogen, combined estrogen-progestin, or tibolone (see [Adverse Reactions]). For all HRT treatments, the excess risk of breast cancer is evident within the first few years of treatment and increases with duration of use, but returns to baseline levels within a few years (up to 5 years) after cessation of treatment. In the MWS study, the relative risk of breast cancer was further increased when conjugated mare's estrogens (CEE) or estradiol (E2) were used sequentially or continuously with a progestogen, regardless of the type of progestogen. There is no evidence that the risk of breast cancer differs with different routes of administration. In the WHI study, continuous treatment with conjugated mare's estrogens and medroxyprogesterone acetate (CEE+MPA) was associated with a slightly larger breast cancer volume and an increased number of regional lymph node metastases compared with placebo. It is unclear whether Ovestin carries the same risk. A recent population-based case-control study of 3345 women with invasive breast cancer compared with 3454 controls showed that estriol was not associated with an increased risk of breast cancer compared with other estrogens. However, the clinical significance of these findings remains unclear. Therefore, it is important to discuss the risk of a possible breast cancer diagnosis with patients and weigh it against the known benefits of HRT. [u]Venous thromboembolism[/u]middot;HRT is associated with an increased relative risk of venous thromboembolic events (VTE, deep vein thrombosis or pulmonary embolism). A randomized controlled trial and epidemiological studies have shown that the risk is 2 to 3 times that of nonusers of HRT. For nonusers of HRT, the estimated number of VTE events in women aged 50 to 59 years and 8 per 1000 women aged 60 to 69 years over 5 years is 3 and 8 per 1000, respectively. The estimated increase in VTE cases for healthy women aged 50 to 59 years and 60 to 69 years who use HRT for 5 years is 2 to 6 (best estimate 4) and 5 to 15 (best estimate 9) per 1000 women, respectively. Such events occur more often within the first year of HRT. The estrogens used in these studies did not include Ovestin, and it is not possible to determine whether Ovestin carries the same risk due to lack of data. middot;In general, recognized risk factors for VTE include personal or family history, severe obesity (BMI>30 kg/m2), and systemic lupus erythematosus (SLE). There is no consensus on the role of varicose veins in the development of VTE. middot;Patients with a history of recurrent VTE or known thrombophilia are at increased risk for VTE. HRT may further increase this risk. Patients with a history of thromboembolism or a strong family history or recurrent spontaneous abortions should be investigated to exclude thrombophilia. The use of HRT in such patients should be considered contraindicated unless thrombophilia factors have been thoroughly evaluated or anticoagulation has been initiated. The benefits and risks of HRT should be carefully considered for women already receiving anticoagulation. middot;The risk of VTE may be temporarily increased by prolonged immobilization, extensive trauma, or major surgery. Precautions should be taken carefully to prevent postoperative VTE in all postoperative patients. Elective surgery, especially abdominal surgery or lower extremity orthopedic surgery, is prone to long-term activity limitation. If possible, temporary suspension of HRT should be considered 4-6 weeks before surgery. If Ovetin is used for "preoperative and postoperative treatment", antithrombotic prophylaxis should be considered. If VTE occurs after starting Ovetin, Ovetin should be discontinued. Patients should be advised to contact their doctor immediately if they find symptoms of possible thromboembolism (such as leg swelling and pain, sudden chest pain, and difficulty breathing). [u]Coronary Artery Disease (CAD) [/u] There is no randomized controlled trial evidence that continuous combined treatment with conjugated estrogens and medroxyprogesterone acetate (MPA) has a cardiovascular benefit. Two large clinical trials (WHI and HERS, the Heart and Estrogen Progesterone Replacement Therapy Study) showed a possible increase in cardiovascular disease incidence in the first year of use, with no overall benefit. However, there are very limited randomized controlled trial data evaluating the effects of other HRT drugs on cardiovascular disease morbidity and mortality. Therefore, it is uncertain whether these trial results can be generalized to other HRT drugs. [u]Stroke[/u]middot;In a large randomized clinical trial (the WHI trial), healthy women who used conjugated estrogens and MPA continuously had an increased risk of ischemic stroke (a secondary endpoint of the trial) during treatment. For women aged 50-59 years and 60-69 years who did not use HRT, the estimated number of strokes over 5 years was 3 per 1000 and 11 per 1000, respectively. The estimated increase in ischemic strokes for women aged 50-59 years and 60-69 years who used conjugated estrogens and MPA continuously for up to five years was 0-3 per 1000 users (best estimate 1) and 1-9 per 1000 users (best estimate 4), respectively. It is uncertain whether this increased risk can be generalized to other HRT drugs. [u]Ovarian cancer[/u]middot;Some epidemiological studies have shown an increased risk of ovarian cancer in women who use estrogen-only HRT for a long time (at least 5-10 years) after total hysterectomy. It is uncertain whether long-term use of combined estrogen-progestin therapy or HRT with low-potency estrogens (such as Ovestin) affects ovarian cancer risk differently from estrogen-only agents. [u]Other conditions[/u]middot;Estrogens may cause fluid retention, so patients with impaired heart function or renal function should be carefully observed. Patients with end-stage renal function should be closely observed because circulating concentrations of the active ingredient of Ovestin are expected to be increased in this setting. middot;Estriol is a weak gonadotropin inhibitor with no other significant effects on the endocrine system. middot;There is no definitive evidence of improvement in cognitive function. There is some evidence from the WHI trial that women who started continuous CEE and MPA combination therapy after age 65 years were at an increased risk of possible dementia. It is unclear whether this finding also applies to younger postmenopausal women or other HRT agents. middot;Ovestin cream contains cetyl and stearyl alcohols, which may cause local skin reactions (such as contact dermatitis).
[Special population use]
Precautions for children: There is still a lack of research data on the effectiveness and safety of this product for children.
Precautions for pregnancy and lactation: It is prohibited to use during pregnancy. There is not enough data to show that the use of this drug during lactation is harmful to infants. However, estriol may enter breast milk and may reduce breast milk secretion.
Precautions for the elderly: See the relevant sections such as indications.
[Storage] Store at 2-25℃, avoid freezing.
[Specification] 15 mg/15 g/vial
[Packaging specification] 15mg:15g
[Expiration date] If stored according to the "Storage" requirements, the validity period is 36 months. After the expiration date, Ovetin cannot be used.
