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Esterified estrogen and methyltestosterone: Drug information

Esterified estrogen and methyltestosterone: Drug information
(For additional information see "Esterified estrogen and methyltestosterone: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Endometrial cancer:

Estrogens have been reported to increase the risk of endometrial carcinoma. Three independent case control studies have reported an increased risk of endometrial cancer in postmenopausal women exposed to exogenous estrogens for prolonged periods. This risk was independent of the other known risk factors for endometrial cancer. These studies are further supported by the finding that incidence rates of endometrial cancer have increased sharply since 1969 in eight different areas of the United States with population-based cancer reporting systems, an increase which may be related to the rapidly expanding use of estrogens during the last decade. The three case control studies reported that the risk of endometrial cancer in estrogen users was about 4.5 to 13.9 times greater than in nonusers. The risk appears to depend on both duration of treatment and on estrogen dose. In view of these findings, when estrogens are used for the treatment of menopausal symptoms, the lowest dose that will control symptoms should be utilized and medication should be discontinued as soon as possible. When prolonged treatment is medically indicated, the patient should be reassessed on at least a semiannual basis to determine the need for continued therapy. Although the evidence must be considered preliminary, one study suggests that cyclic administration of low doses of estrogen may carry less risk than continuous administration; it therefore appears prudent to utilize such a regimen. Close clinical surveillance of all women taking estrogens is important. In all cases of undiagnosed persistent or recurring abnormal vaginal bleeding, adequate diagnostic measures should be undertaken to rule out malignancy. There is no evidence at present that “natural” estrogens are more or less hazardous than “synthetic” estrogens at equiestrogenic doses.

Cardiovascular disease:

This combination does not contain a progestin; it is an estrogen/androgen product. Estrogens with or without progestins should not be used for the prevention of cardiovascular disease. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo.

Breast cancer:

The Women's Health Initiative (WHI) study reported increased risks of invasive breast cancer in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone (2.5 mg) relative to placebo.

Pregnancy:

Estrogens should not be used during pregnancy. The use of female sex hormones, both estrogens and progestogens, during early pregnancy may seriously damage the offspring. It has been shown that females exposed in utero to diethylstilbestrol, a non-steroidal estrogen, have an increased risk of developing in later life a form of vaginal or cervical cancer that is ordinarily extremely rare. This risk has been estimated as not greater than 4 per 1,000 exposures. Furthermore, a high percentage of such exposed women (from 30 to 90 percent) have been found to have vaginal adenosis, epithelial changes of the vagina and cervix. Although these changes are histologically benign, it is not known whether they are precursors of malignancy. Although similar data are not available with the use of other estrogens, it cannot be presumed they would not induce similar changes. Several reports suggest an association between intrauterine exposure to female sex hormones and congenital anomalies, including congenital heart defects and limb reduction defects. One case control study estimated a 4.7-fold increased risk of limb reduction defects in infants exposed in utero to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy, or attempted treatment for threatened abortion). Some of these exposures were very short and involved only a few days of treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat less than 1 per 1,000. In the past, female sex hormones have been used during pregnancy in an attempt to treat threatened or habitual abortion. There is considerable evidence that estrogens are ineffective for these indications, and there is no evidence from well controlled studies that progestogens are effective for these uses. If the combination of estrogens (esterified) and methyltestosterone is used during pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential risks.

Risks vs benefits:

Other doses of conjugated estrogens with medroxyprogesterone and other combinations of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, 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.

Brand Names: US
  • Covaryx;
  • Covaryx HS;
  • EEMT;
  • EEMT HS;
  • Est Estrogens-Methyltest DS;
  • Est Estrogens-Methyltest HS
Pharmacologic Category
  • Estrogen and Androgen Combination
Dosing: Adult
Vasomotor symptoms associated with menopause

Vasomotor symptoms associated with menopause: Adults: Females: Oral: Usual dosage range (based on esterified estrogen component): 0.625 to 1.25 mg once daily administered cyclically (3 weeks on, then 1 week off)

When treating symptoms of menopause, hormone therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals, risk factors, and overall health (NAMS 2017). Adjust dose based on patient response.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Hepatic Impairment: Adult

Use is contraindicated with hepatic dysfunction.

Dosing: Older Adult

Note: Women >65 years of age should be assessed for benefits and risks of treatment; possible adjustments to safer lower-dose and/or route of administration should be considered (ACOG 565 2013; NAMS 2017). The Beers Criteria recommends avoiding systemic estrogen therapy in patients ≥65 years of age (independent of diagnosis or condition) (Beers Criteria [AGS 2019]).

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Covaryx: Esterified estrogens 1.25 mg and methyltestosterone 2.5 mg

Covaryx HS: Esterified estrogen 0.625 mg and methyltestosterone 1.25 mg

EEMT: Esterified estrogens 1.25 mg and methyltestosterone 2.5 mg [contains fd&c blue #1 (brill blue) aluminum lake, quinoline (d&c yellow #10) aluminum lake]

EEMT HS: Esterified estrogen 0.625 mg and methyltestosterone 1.25 mg [contains fd&c blue #1 (brill blue) aluminum lake, quinoline (d&c yellow #10) aluminum lake]

Est Estrogens-Methyltest DS: Esterified estrogens 1.25 mg and methyltestosterone 2.5 mg [contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]

Est Estrogens-Methyltest HS: Esterified estrogen 0.625 mg and methyltestosterone 1.25 mg [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake, methylparaben, propylparaben, quinoline (d&c yellow #10) aluminum lake, sodium benzoate]

Est Estrogens-Methyltest HS: Esterified estrogens 0.625 mg and methyltestosterone 1.25 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine), quinoline yellow (d&c yellow #10)]

Est Estrogens-Methyltest HS: Esterified estrogens 0.625 mg and methyltestosterone 1.25 mg [contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]

Generic: Esterified estrogens 0.625 mg and methyltestosterone 1.25 mg [DSC], Esterified estrogens 1.25 mg and methyltestosterone 2.5 mg

Generic Equivalent Available: US

Yes

Controlled Substance

C-III or nonscheduled (DEA exemption status dependent)

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use: Labeled Indications

Vasomotor symptoms associated with menopause: Treatment of moderate to severe vasomotor symptoms associated with menopause not improved by estrogens alone

Medication Safety Issues
Sound-alike/look-alike issues:

Covaryx HS may be confused with Covera HS

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Older Adult: High-Risk Medication:

Beers Criteria: Estrogens (oral or topical patch products only), with or without progestins, are identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to their carcinogenic potential (breast and endometrium) and lack of cardioprotection or cognitive protection in older women. Low-dose intravaginal estrogen (vaginal creams or tablets) are acceptable for dyspareunia, recurrent lower urinary tract infections, and other vaginal symptoms. Of note, women with a history of breast cancer not responding to non-hormonal therapies are advised to discuss the risks/benefits of low dose vaginal estrogen (estradiol <25 mcg twice weekly) with their healthcare provider (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Estrogens (oral, topical patch, and topical gel products only), with or without progestins, are identified as a high-risk medication in patients 65 years and older on the PQA’s, Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (Ref).

Adverse Reactions

Refer to the Estrogens (Esterified) and the Testosterone monographs.

Contraindications

Undiagnosed abnormal vaginal bleeding; DVT or PE (current or history of); active or history of arterial thromboembolic disease (eg, stroke, MI); carcinoma of the breast (known, suspected or history of), except in appropriately selected patients being treated for metastatic disease; estrogen-dependent tumor; hepatic dysfunction or disease; known or suspected pregnancy or breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Breast cancer: [US Boxed Warning]: Based on data from the Women’s Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA).The risk of breast cancer in postmenopausal patients on hormone therapy may depend upon type of estrogen and/or progestin, dose, timing of therapy initiation, duration of therapy, route of administration, and individual patient characteristics (AACE/ACE [Cobin 2017]; NAMS 2017). Hormone therapy may be associated with increased breast density (NAMS 2017); an increase in abnormal mammogram findings requiring further evaluation has been reported with estrogen alone or in combination with progestin therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs. Information related to androgen use (such as methyltestosterone) is limited (Kabat 2014).

• Dementia: Estrogens with or without progestin should not be used to prevent dementia. In the Women’s Health Initiative Memory Study (WHIMS), an increased incidence of dementia was observed in women ≥65 years of age taking CE alone or in combination with MPA. Because the WHI memory studies were conducted in women ≥65 years of age, it is unknown if these findings apply to younger postmenopausal women. However, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia (AACE [Goodman 2011]; NAMS 2017).

• Endometrial cancer: [US Boxed Warning]: The use of unopposed estrogen in women with an intact uterus is associated with an increased risk of endometrial cancer. The addition of a progestin to estrogen therapy may decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. Adequate diagnostic measures, including endometrial sampling if indicated, should be performed to rule out malignancy in postmenopausal women with undiagnosed abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. The risk of endometrial cancer appears to be dose and duration dependent, greatest with use ≥5 years, and may persist following discontinuation of therapy.

• Endometriosis: Estrogens may exacerbate endometriosis. Malignant transformation of residual endometrial implants has been reported posthysterectomy with unopposed estrogen therapy. Consider adding a progestin in women with residual endometriosis posthysterectomy. This combination product contains an estrogen and androgen; it does not contain a progestin.

• Inherited thrombophilia: Women with inherited thrombophilias (eg, protein C or S deficiency) may have increased risk of venous thromboembolism (DeSancho 2010; van Vlijmen 2011).

• Lipid effects: Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; use with caution in patients with familial defects of lipoprotein metabolism. Testosterone may also alter serum cholesterol; use caution with history of MI or coronary artery disease.

• Ovarian cancer: Available information related to the use of menopausal estrogen or estrogen/progestin therapy and risk of ovarian cancer is inconsistent. If an association is present, the absolute risk is likely rare and may be influenced by duration of therapy (AACE [Goodman 2011]; ES [Stuenkel 2015]; NAMS 2017).

• Polycythemia: Testosterone may increase hematocrit requiring dose adjustment or discontinuation.

• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue if migraine, loss of vision, proptosis, diplopia or other visual disturbances occur; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.

• Virilization: Androgens may cause virilization in women; discontinue if deepening of voice, hirsutism, acne, clitoromegaly, or menstrual irregularities occur.

Disease-related concerns:

• Asthma: Use caution in patients with asthma; may exacerbate disease.

• Carbohydrate intolerance: May impair glucose tolerance; use caution in patients with diabetes. Prior to therapy, consider age, cardiovascular and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]).

• Cardiovascular disease: [US Boxed Warning]: Estrogens with or without progestin should not be used to prevent cardiovascular disease. Using data from the Women’s Health Initiative (WHI) studies, an increased risk of deep vein thrombosis (DVT) and stroke has been reported with CE and an increased risk of DVT, stroke, pulmonary emboli (PE) and myocardial infarction (MI) has been reported with CE with MPA in postmenopausal women. Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of venous thromboembolism (VTE). Risk factors should be managed appropriately; discontinue use immediately if adverse cardiovascular events occur or are suspected. Due to possible lower risk of thrombotic events, transdermal administration may be preferred for treating vasomotor symptoms of menopause in patients with risk factors for cardiovascular disease (AACE/ACE [Cobin 2017]; ACOG 556 2013; ES [Stuenkel 2015]). Use is contraindicated in women with active DVT, PE, arterial thromboembolic disease (stroke and MI), or a history of these conditions.

• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.

• Epilepsy: Use caution with epilepsy; may exacerbate disease.

• Gallbladder disease: Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.

• Hepatic dysfunction: Estrogens are poorly metabolized in patients with hepatic dysfunction. Use caution with a history of cholestatic jaundice associated with prior estrogen use or pregnancy. Discontinue if jaundice develops or if acute or chronic hepatic disturbances occur. Prolonged use of high doses of androgens has been associated with serious hepatic effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, jaundice).

• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease. Use is contraindicated with hepatic disease.

• Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in women with hereditary angioedema.

• Hypocalcemia: Use with caution in patients with severe hypocalcemia.

• Migraine: Use caution with migraine; may exacerbate disease.

• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.

• SLE: Use with caution in patients with SLE; may exacerbate disease.

Concurrent drug therapy issues:

• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.

Special populations:

• Surgical patients: Whenever possible, should be discontinued at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Dosage form specific issues:

• Tartrazine: Some products may contain tartrazine.

Other warnings/precautions:

• Appropriate use: Many warnings are based on data from the Women’s Health Initiative (WHI) studies that evaluated oral estrogen/progestin combinations (CE with or without MPA). Information related to use of estrogen/androgen combinations (esterified estrogens with methyltestosterone) from the WHI study is significantly less (Kabat 2014). In addition, products containing estrogens (esterified) and methyltestosterone have not received pre-market approval by the FDA. Information in this monograph has been expanded beyond the available prescribing information.

• Risks vs benefits: When used for the relief of menopausal symptoms, the benefit-risk of hormone therapy is most favorable if started in patients who have no contraindications to therapy, are <60 years of age, within 10 years of menopause onset, have a favorable lipid profile, and do not have the factor V Leiden genotype or metabolic syndrome. Risk factors for cardiovascular disease should also be considered when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2017). [US Boxed Warning]: Estrogens with or without progestin should be used for the shortest duration possible at the lowest effective dose consistent with treatment goals. Patients should be reevaluated as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women’s Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg with or without MPA 2.5 mg relative to placebo in postmenopausal women. Other combinations and dosage forms of estrogens and progestins were not studied. Outcomes reported from clinical trials using CE with or without MPA should be assumed to be similar for other doses and other dosage forms of estrogens and progestins until comparable data becomes available.

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Blood Glucose Lowering Effects: Androgens may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Ajmaline: Androgens may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination

Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

C1 inhibitors: Androgens may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the fluid-retaining effect of Androgens. Risk C: Monitor therapy

Cosyntropin: Estrogen Derivatives may diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Androgens may enhance the hepatotoxic effect of CycloSPORINE (Systemic). Androgens may increase the serum concentration of CycloSPORINE (Systemic). Management: Consider avoiding concomitant use of androgens and cyclosporine. If concomitant use is unavoidable, monitor serum cyclosporine concentrations and for signs and symptoms of hepatotoxicity. Cyclosporine dose reductions may be required. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Risk C: Monitor therapy

Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Risk X: Avoid combination

Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Growth Hormone Analogs: Estrogen Derivatives may diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification

Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Risk X: Avoid combination

Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Hydrocortisone (Systemic): Estrogen Derivatives may increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy

Hypertension-Associated Agents: May enhance the hypertensive effect of Androgens. Risk C: Monitor therapy

Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Risk C: Monitor therapy

Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination

LamoTRIgine: Estrogen Derivatives may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Risk C: Monitor therapy

Melatonin: Estrogen Derivatives may increase the serum concentration of Melatonin. Risk C: Monitor therapy

MetyraPONE: Estrogen Derivatives may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider therapy modification

Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Risk X: Avoid combination

Pomalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Pomalidomide. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Estrogen Derivatives. Protease Inhibitors may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Risk C: Monitor therapy

Tacrolimus (Systemic): Estrogen Derivatives may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy

Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy

Tranexamic Acid: Estrogen Derivatives may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Androgens may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Monitor for increased effects of vitamin K antagonists if an androgen is initiated/dose increased, or decreased effects if androgen is discontinued/dose decreased. Significant reductions in vitamin K antagonist dose are likely required. Risk D: Consider therapy modification

Pregnancy Considerations

[US Boxed Warning]: Estrogens should not be used during pregnancy. This product is specifically contraindicated during pregnancy.

Refer to the Estrogens (Esterified) monograph and the Testosterone monograph for additional information.

Breastfeeding Considerations

This product is specifically contraindicated in breastfeeding women.

Refer to the Estrogens (Esterified) monograph and the Testosterone monograph for additional information.

Monitoring Parameters

Prior to therapy, baseline risk for breast cancer and CVD. During therapy, liver function tests; signs of virilization (eg, hirsutism, acne, deepening of voice, clitoromegaly); age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer); serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL); TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement); efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).

Mechanism of Action

Conjugated estrogens: Activate estrogen receptors (DNA protein complex) located in estrogen-responsive tissues. Once activated, regulate transcription of certain genes leading to observed effects.

Testosterone: Increases synthesis of DNA, RNA, and various proteins in target tissues

Pharmacokinetics

Refer to the Estrogens (Esterified) and the Testosterone monographs.

Pricing: US

Tablets (Covaryx HS Oral)

0.625-1.25 mg (per each): $3.60

Tablets (Covaryx Oral)

1.25-2.5 mg (per each): $3.60

Tablets (EEMT HS Oral)

0.625-1.25 mg (per each): $4.78

Tablets (EEMT Oral)

1.25-2.5 mg (per each): $4.78

Tablets (Est Estrogens-Methyltest Oral)

1.25-2.5 mg (per each): $4.78 - $4.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Estratest (CA)


For country code abbreviations (show table)
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