Premarin

Natural conjugated estrogens.

Premarin (conjugated estrogens tablets) for oral administration contains a mixture of conjugated estrogens obtained exclusively from natural sources, occurring as the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares' urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate. It contains as concomitant components, as sodium sulfate conjugates, 17α-dihydroequilin, 17α-estradiol, and 17β- dihydroequilin.
Excipients/Inactive Ingredients: Tablet cores: Lactose Monohydrate Spray Dried, Hypromellose 2208, K100M, Microcrystalline Cellulose, Magnesium stearate, Purified water.
Tablet coating: Sucrose, Microcrystalline Cellulose, Hydroxypropyl Cellulose, Hypromellose, 2910, E6, Hypromellose 2910, E15, Polyethylene Glycol 400, Purified water, Opadry Green 15B21511, Opadry Maroon 03B16083, Carnauba Wax, Opacode WB NS-78-18011, White Ink.

Pharmacology: Pharmacodynamics: Currently, there are no pharmacodynamic data known for CE alone.
Mechanism of Action: Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in post-menopausal women.
Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in post-menopausal women.
Effects on vasomotor symptoms: In the first year of the Health and Osteoporosis, Progestin and Estrogen (HOPE) Study, a total of 2,805 post-menopausal women (average age 53.3 ± 4.9 years) were randomly assigned to one of eight treatment groups, receiving either placebo or conjugated estrogens, with or without medroxyprogesterone acetate. Efficacy for vasomotor symptoms was assessed during the first 12 weeks of treatment in a subset of symptomatic women (n = 241) who had at least seven moderate-to-severe hot flushes daily, or at least 50 moderate-to-severe hot flushes during the week before randomization. With CE (0.3 mg, 0.45 mg, and 0.625 mg tablets), the decrease of both the frequency and severity of moderate-to-severe vasomotor symptoms was shown to be statistically improved compared with placebo at weeks 4 and 12. Table 1 shows the observed mean number of hot flushes in the CE 0.3 mg, 0.45 mg, and 0.625 mg and placebo treatment groups over the initial 12-week period. (See Table 1.)

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Effects on vulvar and vaginal atrophy: Results of vaginal maturation indexes at cycles 6 and 13 showed that the differences from placebo were statistically significant (p < 0.001) for all treatment groups.
Effect on bone mineral density: Health and Osteoporosis, Progestin and Estrogen (HOPE): Study The HOPE study was a double-blind, randomized, placebo/active-drug-controlled, multicenter study of healthy post-menopausal women with an intact uterus. Subjects (mean age 53.3 ± 4.9 years) were 2.3 ± 0.9 years on average since menopause and took one 600 mg tablet of elemental calcium (Caltrate) daily. Subjects were not given Vitamin D supplements. They were treated with CE 0.625 mg, 0.45 mg, 0.3 mg, or placebo. Prevention of bone loss was assessed by measurement of bone mineral density (BMD), primarily at the anteroposterior lumbar spine (L2 to L4). Secondarily, BMD measurements of the total body, femoral neck, and trochanter were also analyzed. Serum osteocalcin, urinary calcium, and N telopeptide were used as bone turnover markers (BTM) at cycles 6, 13, 19, and 26.
Intent-to-treat subjects: All active treatment groups showed significant differences from placebo in each of the four BMD endpoints at cycles 6, 13, 19, and 26. The percent changes from baseline to final evaluation are shown in Table 2. (See Table 2.)

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The bone turnover markers serum osteocalcin and urinary N-telopeptide significantly decreased (p < 0.001) in all active-treatment groups at cycles 6, 13, 19, and 26 compared with the placebo group. Larger mean decreases from baseline were seen with the active groups than with the placebo group. Significant differences from placebo were seen less frequently in urine calcium.
Effects on female hypogonadism: CE Tablets: In clinical studies of delayed puberty due to female hypogonadism, breast development was induced by doses as low as 0.15 mg. The dosage may be gradually titrated upward at 6 to 12-month intervals as needed to achieve appropriate bone age advancement and eventual epiphyseal closure. Available data suggest that chronic dosing with 0.625 mg is sufficient to induce artificial cyclic menses with sequential progestin treatment and to maintain bone mineral density after skeletal maturity is achieved.
Women's Health Initiative Studies (WHI): The Women's Health Initiative (WHI) enrolled approximately 27,000 predominantly healthy post-menopausal women in two substudies to assess the risks and benefits of conjugated estrogens (CE) [0.625 mg daily] alone or in combination with MPA [0.625 mg/2.5 mg daily] compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) defined as non-fatal myocardial infarction (MI), silent MI and CHD death, with invasive breast cancer as the primary adverse outcome. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer (only in the CE plus MPA substudy), colorectal cancer, hip fracture, or death due to other causes. The study did not evaluate the effects of CE alone or CE plus MPA on menopausal symptoms.
WHI Estrogen-alone Substudy: The WHI estrogen-alone substudy was stopped early because an increased risk of stroke was observed, and it was deemed that no further information would be obtained regarding the risks and benefits of estrogen alone in predetermined primary endpoints.
Results of the estrogen-alone substudy, which included 10,739 women (average age of 63.6 years, range 50 to 79; 75.3% White, 15.1% Black, 6.1% Hispanic, 3.6% Other), after an average follow-up of 7.1 years, are presented in the table below.
In the estrogen-alone substudy of WHI, there was no significant overall effect on the relative risk (RR) of CHD (RR 0.95, 95% nominal confidence interval [nCI] 0.78-1.16); a slightly elevated RR of CHD was reported in the early follow-up period and diminished over time. There was no significant effect on the RR of invasive breast cancer (RR 0.80, 95% nCI 0.62-1.04) or colorectal cancer (RR 1.08, 95% nCI 0.75-1.55) reported. Estrogen use was associated with a statistically significant increased risk of stroke (RR 1.33, 95% nCI 1.05-1.68) and deep vein thrombosis (DVT) (RR 1.47, 95% nCI 1.06-2.06). The RR of PE (RR 1.37, 95% nCI 0.90-2.07) was not significantly increased. A statistically significant reduced risk of hip, vertebral and total fractures was reported with estrogen use (RR 0.65, 95% nCI 0.45-0.94), (RR 0.64, 95% nCI 0.44-0.93), and (RR 0.71, 95% nCI 0.64-0.80), respectively. The estrogen-alone substudy did not report a statistically significant effect on death due to other causes (RR 1.08, 95% nCI 0.88-1.32) or an effect on overall mortality risk (RR 1.04, 95% nCI 0.88-1.22). These confidence intervals are unadjusted for multiple looks and multiple comparisons. (See Table 3.)

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Primary results of the Estrogen-alone substudy stratified by age at baseline is described in the following table. (See Table 4.)

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Timing of initiation of estrogen therapy from the start of menopause may affect the overall risk-benefit profile. The WHI estrogen-alone substudy stratified by age showed in women 50-59 years of age, a non-significant trend towards reduced risk for CHD and overall mortality compared with placebo in women who initiated hormone therapy closer to menopause than those initiating therapy more distant from menopause.
Women's Health Initiative Memory Study: The estrogen-alone Women's Health Initiative Memory Study (WHIMS), an ancillary study of WHI, enrolled 2947 predominantly healthy hysterectomized post-menopausal women 65 years of age and older (45 percent were 65 to 69 years of age; 36 percent were 70 to 74 years of age; and 19 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg) in the incidence of probable dementia (primary outcome) compared to placebo.
After an average follow-up of 5.2 years, the relative risk of probable dementia for CE alone vs. placebo was 1.49 (95% CI 0.83-2.66). The absolute risk of probable dementia for CE alone vs. placebo was 37 vs. 25 cases per 10,000 women-years. Probable dementia as defined in this study included Alzheimer's disease (AD), vascular dementia (VaD) and mixed types (having features of both AD and VaD). The most common classification of probable dementia in both the treatment and placebo groups was AD. Since the substudy was conducted in women aged 65 to 79 years, it is unknown whether these findings apply to younger post-menopausal women (see WHIM Study as previously mentioned and Dementia under Precautions).
Pharmacokinetics: Absorption: Conjugated estrogens are soluble in water and are well-absorbed from the gastrointestinal tract after release from the drug formulation. The CE tablet releases conjugated estrogens slowly over several hours. Maximum plasma concentrations are achieved approximately 6-10 hours following CE tablet administration. The estrogens are generally eliminated in near-parallel fashion, with half-lives ranging from 10-20 hours, when corrected for endogenous concentrations as needed.
Distribution: The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentration in the sex hormone target organs. Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.
Metabolism: Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In post-menopausal women a significant proportion of the circulating estrogens exists as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.
Excretion: Estradiol, estrone, and estriol are excreted in the urine, along with glucuronide and sulfate conjugates.
Special Populations: No pharmacokinetic studies were conducted in special populations, including patients with renal or hepatic impairment.
Toxicology: Preclinical Safety Data: Not applicable.

Moderate to severe vasomotor symptoms associated with estrogen deficiency.
Prevention and management of osteoporosis associated with estrogen deficiency. When prescribing solely for the prevention of post-menopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered appropriate. When prescribing solely for the management of post-menopausal osteoporosis, non-estrogen medications should be first considered.
Atrophic vaginitis and atrophic urethritis. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Female hypoestrogenism.
ERT and HRT should not be initiated or continued to prevent coronary heart disease (see also Cardiovascular risk and DEMENTIA).
The benefits and risks of ERT and HRT must always be carefully weighed, including consideration of the emergence of risks as therapy continues (see SPECIAL WARNINGS under Precautions). Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. In the absence of comparable data, the risks of HRT should be assumed to be similar to all estrogens and estrogen/progestin combinations.

The benefits and risks of estrogen therapy (ET) must always be carefully weighed, including consideration of the emergence of risks as therapy continues (see Precautions). Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
If an estrogen is prescribed for a post-menopausal woman with a uterus, the addition of a progestin may be appropriate (see Malignant Neoplasms under Precautions). In some cases, hysterectomized women with a history of endometriosis may need a progestin (see Exacerbation of other conditions under Precautions).
Tablets should be taken whole; do not divide, crush, chew, or dissolve tablets in mouth.
Vasomotor Symptoms and/or Vulvar and Vaginal Atrophy: Consider topical vaginal products when treating solely for vulvar and vaginal atrophy.
Prevention/Management of Post-menopausal Osteoporosis: When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.
Female Hypoestrogenism: Administer cyclically (e.g., three weeks on and one week off).
Usual Dosage Range: VASOMOTOR SYMPTOMS, ATROPHIC VAGINITIS AND ATROPHIC URETHRITIS ASSOCIATED WITH ESTROGEN DEFICIENCY: 0.3 mg - 1.25 mg daily.
OSTEOPOROSIS: Generally, women should be started at 0.3 mg Premarin daily. Subsequent dosage adjustment may be made based upon the individual clinical and bone mineral density responses. This dose should be periodically reassessed by the healthcare provider.
PREMARIN therapy may be given continuously, with no interruption in therapy, or in cyclical regimens (regimens such as 25 days on drug followed by 5 days off drug), as is medically appropriate on an individualized basis.
FEMALE HYPOESTROGENISM: 0.3 mg - 1.25 mg daily, administered cyclically (e.g., three weeks on and one week off). Doses are adjusted depending on the severity of symptoms and responsiveness of the endometrium.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Estrogen treatment of prepubertal girls induces premature breast development and vaginal cornification, and may induce uterine bleeding.
Since large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, hormonal therapy should not be started before epiphyseal closure has occurred in order not to compromise final growth.
Use in Elderly Patients: There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estrogens to determine whether those over 65 years of age differ from younger subjects in their response to estrogens.
The Women's Health Initiative Study (WHI): In the WHI estrogen-alone substudy (daily CE [0.625 mg] versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age (see Pharmacology: Pharmacodynamics: WHI Studies under Actions).
The Women's Health Initiative Memory Study (WHIMS): In the WHIMS of post-menopausal women 65 to 79 years of age, there was increased risk of developing probable dementia in women receiving estrogen alone when compared to placebo. It is unknown whether this finding applies to younger post-menopausal women (see Pharmacology: Pharmacodynamics: WHIM Study under Actions and Dementia under Precautions).

Symptoms of overdosage of estrogen-containing products in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue; withdrawal bleeding may occur in females. There is no specific antidote and further treatment if necessary should be symptomatic.

Known,suspected, or history of breast cancer.
Known or suspected estrogen-dependent neoplasia (e.g., endometrial cancer, endometrial hyperplasia).
Known or suspected pregnancy (see Fertility, Pregnancy and Lactation under Use in Pregnancy & Lactation).
Undiagnosed abnormal uterine bleeding.
Active or history of confirmed arterial thromboembolic disease (e.g., stroke, myocardial infarction) or venous thromboembolism (such as deep venous thrombosis, pulmonary embolism).
Hypersensitivity to any component of this medication.
Active or chronic liver dysfunction or disease.
Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency).

Special Warnings: General: Combined Estrogen and Progestin Therapy: There are additional and/or increased risks that may be associated with the use of combination estrogen-plus-progestin therapy compared with using estrogen-alone regimens. These include an increased risk of myocardial infarction, pulmonary embolism, invasive breast cancer and ovarian cancer.
Cardiovascular risk: ET has been reported to increase the risk of stroke and deep venous thrombosis (DVT).
Patients who have risk factors for thrombotic disorders should be kept under careful observation.
Patients who are at risk of developing migraines with aura may be at risk of ischemic stroke and should be kept under careful observation.
Stroke: In the WHI estrogen-alone-substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) compared to women receiving placebo (45 vs. 33 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted.
Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg) versus those receiving placebo (18 versus 21 per 10,000 women-years).
Should a stroke occur or be suspected, estrogens should be discontinued immediately (see Pharmacology: Pharmacodynamics under Actions).
Venous thromboembolism (VTE): In the estrogen-alone substudy of WHI, the increased risk of deep venous thrombosis (DVT) was reported to be statistically significant (23 vs. 15 per 10,000 person-years). The risk of pulmonary embolism (PE) was reported to be increased, although it did not reach statistical significance. The increase in venous thromboembolism (VTE,DVT and PE) risk was demonstrated during the first two years (30 vs. 22 per 10,000 person-years).
Should a VTE occur or be suspected, estrogens should be discontinued immediately (see Pharmacology: Pharmacodynamics under Actions).
If visual abnormalities develop, discontinue estrogens pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be withdrawn. Retinal vascular thrombosis has been reported in patients receiving estrogens with or without progestins.
If feasible, estrogens should be discontinued at least four to six weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Malignant Neoplasms: Endometrial cancer: The use of unopposed estrogens in women with an intact uterus has been associated with an increased risk of endometrial cancer (see Pharmacology: Pharmacodynamics under Actions and Exacerbation of other conditions as follows).
The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after ET is discontinued. Adding a progestin to post-menopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer (see General as previously mentioned).
Clinical surveillance of all women taking estrogen or estrogen-plus-progestin combinations is important. Adequate diagnostic measures should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal uterine bleeding.
Breast Cancer: Studies involving the use of estrogens by post-menopausal women have reported inconsistent results on the risk of breast cancer. The most important randomized clinical trial providing information about this issue is the Women's Health Initiative (WHI) (see Pharmacology: Pharmacodynamics under Actions). In the estrogen-alone substudy of WHI, after an average of 7.1 years of follow-up, CE (0.625 mg daily) was not associated with an increased risk of invasive breast cancer.
Some observational studies have reported an increased risk of breast cancer for estrogen-alone therapy after several years of use. The risk increased with duration of use, and appeared to return to baseline within approximately five years after stopping treatment (only the observational studies have substantial data on risk after stopping).
The use of estrogen has been reported to result in an increase in abnormal mammograms requiring further evaluation.
Ovarian cancer: In some epidemiologic studies, the use of estrogen therapy has been associated with an increased risk of ovarian cancer over multiple years of use. Other epidemiologic studies have not found these associations.
Dementia: The estrogen-alone arm of the Women's Health Initiative Memory Study (WHIMS), an ancillary study of WHI that enrolled post-menopausal women between the ages of 65-79 reported a relative risk (HR) of probable dementia for conjugated estrogens alone versus placebo of 1.49 [HR 1.49 (95% CI 0.83-2.66)] (see Pharmacology: Pharmacodynamics under Actions).
It is unknown whether these findings apply to younger post-menopausal women.
Gallbladder Disease: A 2 to 4-fold increase in the risk of gallbladder disease requiring surgery in women receiving ET has been reported.
Hypercalcemia: Administration of estrogens may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If this occurs, the drug should be stopped and appropriate measures taken to reduce the serum calcium level.
Palliative therapy in men: Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.
Immune System: Angioedema: Exogeneous estrogens may induce or exacerbate symptoms of angioedema, particularly in patients with hereditary angioedema.
Fluid retention: Because estrogens may cause some degree of fluid retention, patients with conditions, which might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed.
Hypertriglyceridemia: In the Health and Osteoporosis, Progestin and Estrogen (HOPE) Study, the mean percent increases from baseline in serum triglycerides after one year of treatment with CE 0.625 mg, 0.45 mg 0.3 mg and placebo were 34.2, 30.2, 25.0, and 10.8, respectively.
Caution should be exercised in patients with pre-existing hypertriglyceridemia since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with estrogen therapy in this population.
Impaired liver function and history of cholestatic jaundice: For patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued. Estrogens may be poorly metabolized in patients with impaired liver function.
Elevated blood pressure: In a small number of case reports, substantial increases in blood pressure during ET have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial a generalized effect of ET on blood pressure was not seen.
Exacerbation of other conditions: Estrogen therapy may cause an exacerbation of asthma, epilepsy, migraine with or without aura, otosclerosis, porphyria, systemic lupus erythematosus, and hepatic hemangiomas, and should be used with caution in women with these conditions.
Endometriosis may be exacerbated with administration of estrogen therapy. A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Hypocalcemia: Estrogens should also be used with caution in individuals with disease that can predispose to severe hypocalcemia.
Hypothyroidism: Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Patients dependent on thyroid hormone therapy, who are receiving estrogens, may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range (see Interactions).
Laboratory monitoring: Estrogen administration should be guided by clinical response rather than by hormone levels (e.g., estradiol, FSH).
Effects on Ability to Drive and Use Machines: No studies on the effect of ability to drive or use machines have been performed.

Pregnancy: Estrogens should not be used during pregnancy (see Contraindications).
If pregnancy occurs during medication with Estrogens treatment should be withdrawn immediately.
Lactation: Estrogens should not be used during lactation.
Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of breast milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving the drug. Caution should be exercised when estrogens are administered to a nursing woman.

Adverse reactions are listed in the Table in CIOMS frequency categories: Very Common: ≥10%, Common: ≥1% and <10%, Uncommon: ≥0.1% and <1%, Rare: ≥0.01% and <0.01%, Very rare: <0.01%. (See Table 5.)

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Data from a drug-drug interaction study involving conjugated estrogens and medroxyprogestrone acetate indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are co-administered. Other clinical drug-drug interaction studies have not been conducted with conjugated estrogens.
In vitro and in vivo studies have shown that estrogens, are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's Wort (Hypericum perforatum) preparations, phenobarbital, phenytoin, carbamazepine, rifampicin and dexamethosone may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4, such as cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects.
Interference with Laboratory and Other Diagnostic Tests: Laboratory Test Interactions: Increased platelet count; decreased levels of antithrombin III, increased plasminogen antigen and activity.
Estrogens increase thyroid-binding globulin (TBG) leading to increased circulating total 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 unaltered.
Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) leading to increased circulating corticosteroid and sex steroids, respectively. Free or biologically active hormone concentrations may be decreased.
Increased plasma HDL and HDL₂ cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglyceride levels.
Impaired glucose tolerance.
The response to metyrapone may be reduced.

Incompatibilities: Not applicable.

Do not store above 30°C.

Oestrogens, Progesterones & Related Synthetic Drugs

G03CA57 - conjugated estrogens ; Belongs to the class of natural and semisynthetic estrogens used in estrogenic hormone preparations.

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