Premarin 0.625 mg Coated Tablets – Summary of Product Characteristics (SmPC) – (emc)

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that negatively affect quality of life. In all cases, a careful assessment of the risks and benefits should be performed at least once a year, and hrt should only be continued as long as the benefit outweighs the risk.

Evidence on the risks associated with HRT in the treatment of premature menopause is limited. however, due to the low level of absolute risk in younger women, the balance of benefits and risks for these women may be more favorable than for older women.

1. medical examination/follow-up

Before starting or reinstating HRT, a complete personal and family medical history should be taken. the physical examination (including pelvic and breast) should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups of a frequency and nature adapted to each woman are recommended. women should be told what changes in their breasts should be reported to their doctor or nurse (see ‘breast cancer’ below). investigations, including appropriate imaging tools, e.g. mammography, should be performed in accordance with currently accepted screening practices, modified according to the clinical needs of the individual.

2. conditions that need supervision

If any of the following conditions are present, have previously occurred, and/or have been aggravated during pregnancy or prior hormonal treatment, the patient should be closely monitored. it should be borne in mind that these conditions may recur or aggravate during treatment with premarin, in particular:

leiomyoma (uterine fibroids) or endometriosis

risk factors for thromboembolic disorders (see below)

risk factors for estrogen-dependent tumors (eg, first-degree inheritance for breast cancer)


liver disorders (for example, hepatic adenoma)

diabetes mellitus with or without vascular involvement


migraine or (severe) headaches

systemic lupus erythematosus (SLE)

history of endometrial hyperplasia (see below)




3. reasons for immediate discontinuation of therapy

Therapy should be discontinued if a contraindication is discovered and in the following situations:

jaundice or impaired liver function

significant increase in blood pressure

new onset of migraine headache


4. endometrial hyperplasia and carcinoma

In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma is increased when estrogens alone are administered for prolonged periods. the reported increased risk of endometrial cancer among oestrogen-only users ranges from 2- to 12-fold compared with non-users, depending on duration of treatment and estrogen dose (see section 4.8). after stopping treatment, the risk may remain elevated for at least 10 years.

The addition of a progestin for at least 12 days per month/28-day cycle or continuous combined estrogen and progestin therapy in non-hysterectomized women prevents the excess risk associated with estrogen-only HRT.

For oral doses of conjugated equine estrogens >0.625 mg, the endometrial safety of added progestogens has not been demonstrated. the reduced risk to the endometrium must be weighed against the increased risk of breast cancer from added progestagen (see ‘breast cancer’ below and section 4.8).

Breakthrough bleeding and spotting may occur during the first few months of treatment. if breakthrough bleeding or spotting occurs after a period of treatment, or continues after treatment has been stopped, the reason should be investigated, which may include an endometrial biopsy to rule out endometrial malignancy.

Unopposed estrogen stimulation can lead to premalignant or malignant transformation in residual foci of endometriosis. therefore, the addition of progestins to estrogen replacement therapy should be considered in women who have had a hysterectomy for endometriosis, if they are known to have residual endometriosis (but see above).

5. breast cancer

Overall evidence shows an increased risk of breast cancer in women taking combined estrogen-progestin or estrogen-only HRT, which depends on the duration of HRT.

the women’s health initiative (whi) trial found no increased risk of breast cancer in hysterectomized women using estrogen-only thr. observational studies have mainly reported a small increased risk of being diagnosed with breast cancer that is lower than that found in users of combined estrogen and progestogen (see section 4.8).

The results of a large meta-analysis showed that after stopping treatment, the excess risk will decrease over time and the time needed to return to baseline depends on the duration of prior hrt use. when hrt has been taken for more than 5 years, the risk may persist for 10 years or more.

hrt, especially combined estrogen and progestin therapy, increases the density of mammographic images, which may adversely affect radiological detection of breast cancer.

6. ovarian cancer

Ovarian cancer is much rarer than breast cancer.

Epidemiologic evidence from a large meta-analysis suggests a slightly increased risk in women taking estrogen-only or combined estrogen-progestin HRT, becoming apparent within 5 years of use and decreasing over time thereafter to suspend it.

some other studies, including the whi trial, suggest that the use of combined hrs may be associated with a similar or slightly lower risk (see section 4.8).

7. Venous thromboembolism

Hormone replacement therapy (HRT) is associated with a 1.3- to 3-fold increased risk of developing venous thromboembolism (VTE), ie deep vein thrombosis or pulmonary embolism. the occurrence of such an event is more likely in the first year of hrt than later (see section 4.8).

Patients with a history of VTE or known thrombophilic states are at increased risk of VTE. hrt can increase this risk. therefore, HRT is contraindicated in these patients (see section 4.3). significant personal or family history of thromboembolism or recurrent spontaneous abortion should be investigated to exclude a thrombophilic predisposition.

Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index > 30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE) and cancer. there is no consensus on the possible role of varicose veins in vte.

As in all postoperative patients, scrupulous attention should be paid to prophylactic measures to prevent tea after surgery. If prolonged immobilization is likely to follow elective surgery, particularly lower extremity abdominal or orthopedic surgery, it is recommended that HRT be temporarily discontinued 4 to 6 weeks prior. treatment should not be restarted until the woman is fully mobilized.

in women with no personal history of vt but with a first-degree relative with a history of thrombosis at a young age, screening may be offered after careful counseling about its limitations (screening only identifies a proportion of thrombophilic defects) . if a thrombophilic defect is identified that segregates with thrombosis in family members or if the defect is “severe” (eg, antithrombin, protein s, or protein c deficiencies or a combination of defects), hrt is contraindicated. /p>

women already on chronic anticoagulant therapy require careful consideration of the risk-benefit ratio of hrt use.

If vte develops after initiation of therapy, the drug should be discontinued. Patients should be instructed to contact their physicians immediately when they become aware of possible thromboembolic symptoms (eg, painful swelling of a leg, sudden chest pain, dyspnea).

8. Coronary artery disease (CAD)

There is no evidence from randomized controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined estrogen-progestin or estrogen-only HRT. randomized controlled data found no increased risk of CAD in hysterectomized women using estrogen-only therapy.

9. ischemic stroke

Combined estrogen-progestin and estrogen-only therapy is associated with up to a 1.5-fold increase in the risk of ischemic stroke. the relative risk does not change with age or time since menopause. however, since the baseline risk of stroke is highly age dependent, the overall risk of stroke in women using ths will increase with age (see section 4.8).

In the estrogen-alone whi substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age who received daily ce (0.625 mg) compared with women who received placebo (45 versus 33 per 10,000 woman-years). the increased risk was demonstrated in the first year and persisted. Subgroup analyzes of women aged 50 to 59 years do not suggest an increased risk of stroke for women receiving CE (0.625 mg) versus those receiving placebo (18 versus 21 per 10,000 woman-years).

other conditions

10. estrogens can cause fluid retention and therefore patients with cardiac or renal dysfunction should be carefully observed.

11. Estrogen use may influence laboratory results of certain endocrine and liver enzyme tests.

Estrogens increase thyroid binding globulin (tbg), leading to an increase in total circulating thyroid hormone, as measured by protein-bound iodine (pbi), t4 levels (by column or by radioimmunoassay) or t3 levels (by radioimmunoassay). t3 resin uptake is decreased, reflecting the elevated tbg. free t4 and free t3 concentrations are unchanged.

Other binding proteins may be elevated in serum, i.e. corticosteroid binding globulin (cbg), sex hormone binding globulin (shbg), leading to increased circulating corticosteroids and sex steroids, respectively. the concentrations of free or biologically active hormones do not change. other plasma proteins may increase (angiotensinogen/renin substrate, alpha-i-antitrypsin, ceruloplasmin).

Some patients who are dependent on thyroid hormone replacement therapy may need higher doses to keep their free thyroid hormone levels in an acceptable range. therefore, patients should have their thyroid function monitored more frequently when starting concurrent treatment to maintain their free thyroid hormone levels in an acceptable range.

12. Impaired glucose tolerance may occur in patients taking estrogens and therefore diabetic patients should be carefully observed while receiving hormone replacement therapy.

13. There is an increased risk of gallbladder disease in women taking HRT (see Conditions Needing Supervision).

14. Women with pre-existing hypertriglyceridemia should be closely followed during estrogen replacement or hormone replacement therapy, as rare cases of large increases in plasma triglycerides leading to pancreatitis have been reported with estrogen therapy in this condition.

15. estrogens should be used with caution in people with severe hypocalcemia.

16. hrt use does not improve cognitive function. there is some evidence from the whi trial of an increased risk of probable dementia in women who start continuous combined or estrogen-only hrt after age 65 years.

17. exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema.

18. laboratory monitoring

Estrogen administration should be guided by clinical response rather than hormone levels (eg, estradiol, fsh).

19. This product contains lactose monohydrate and sucrose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, lapp lactase deficiency, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine.

Content Creator Zaid Butt joined Silsala-e-Azeemia in 2004 as student of spirituality. Mr. Zahid Butt is an IT professional, his expertise include “Web/Graphic Designer, GUI, Visualizer and Web Developer” PH: +92-3217244554

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