Estropipate, Esterified Estrogens

Name: Estropipate, Esterified Estrogens

Estropipate, Esterified Estrogens Dosage and Administration

General

  • A progestin generally is added to estrogen therapy (HRT) in women with an intact uterus.a Addition of a progestin for ≥10 days per cycle of estrogen administration or daily with estrogen reduces incidence of endometrial hyperplasia and attendant risk of endometrial carcinoma in women with an intact uterus.a

ERT is appropriate in women who have undergone a hysterectomy (avoids unnecessary exposure to progestins).106 107 108

Administration

Administer estropipate and esterified estrogens orally.106 107 108

Estrogen therapy generally is administered in a continuous daily dosage regimen or, alternatively, in a cyclic regimen.106 107 108 When administered cyclically, estrogen usually is given once daily for 3 weeks followed by 1 week without the drug; regimen is repeated as necessary.106 107 108

Oral Administration

Administer orally one or more times daily.106 107 108

When estropipate or esterified estrogens is used for management of vasomotor symptoms, initiate treatment at any time in women who have not menstruated within the previous 2 months; if patient is menstruating, start cyclic administration on day 5 of cycle.106 107

Dosage

Individualize dosage according to the condition being treated and the tolerance and therapeutic response of the patient.106 107 108

To minimize risk of adverse effects, use the lowest possible effective dosage.106 107 108 c Because of the potential increased risk of cardiovascular events, breast cancer, and venous thromboembolic events, limit estrogen and estrogen/progestin therapy to the lowest effective doses and shortest duration of therapy consistent with treatment goals and risks for the individual woman.106 107 108

Periodically reevaluate estrogen and estrogen/progestin therapy (i.e., at 3- to 6-month intervals).106 107 108

Adults

Estrogen Replacement Therapy Vasomotor Symptoms Oral

Estropipate: 0.75–6 mg daily in a cyclic regimen.106

Esterified estrogens: 1.25 mg daily in a cyclic regimen.107

Esterified estrogens in fixed combination with methyltestosterone: Esterified estrogens 0.625 mg with methyltestosterone 1.25 mg daily in a cyclic regimen (3 weeks on, 1 week off).108 Alternatively, esterified estrogens 1.25 mg with methyltestosterone 2.5 mg daily in a cyclic regimen.108

Vulvar and Vaginal Atrophy Oral

Estropipate: 0.75–6 mg daily in a cyclic regimen.106

Esterified estrogens: 0.3–≥1.25 mg daily in a cyclic regimen.107

Osteoporosis Prevention in Postmenopausal Women Oral

Estropipate: 0.75 mg daily in a cyclic regimen (25 days on, 6 days off).106

Hypoestrogenism Female Hypogonadism Oral

Estropipate: 1.5–9 mg daily for 3 weeks followed by 8–10 days without the drug; if menstruation does not occur by the end of the 8- to 10-day drug-free period, repeat the same dosage schedule.106 Number of courses required to induce menstruation varies depending on endometrial responsiveness.106 If satisfactory withdrawal bleeding does not occur, may administer an oral progestin concomitantly during the third week of the cycle.106

Esterified estrogens: 2.5–7.5 mg daily in divided doses for 20 days, followed by 10 days without the drug.107 Number of courses required to induce menstruation varies depending on endometrial responsiveness.107 If menstruation does not occur by the end of the first complete cycle, repeat the same dosage schedule.107 If menstruation occurs before the end of the 10-day drug-free period, initiate estrogen-progestin regimen with esterified estrogens 2.5–7.5 mg given daily in divided doses for 20 days; administer oral progestin during the last 5 days of esterified estrogens administration.107 If menstruation begins before the estrogen-progestin regimen is completed, discontinue therapy and then reinstitute on the fifth day of menstruation.107

Female Castration or Primary Ovarian Failure Oral

Estropipate: 1.5–9 mg daily for 3 weeks, followed by 8–10 days without the drug.106 Adjust dosage according to severity of symptoms and therapeutic response.106

Esterified estrogens: 1.25 mg daily in a cyclic regimen.107 Adjust dosage according to severity of symptoms and therapeutic response.107

Metastatic Breast Carcinoma Oral

Esterified estrogens: 10 mg 3 times daily for ≥3 months.107

Prostate Carcinoma Oral

Esterified estrogens: 1.25–2.5 mg 3 times daily.107

Interactions for Estropipate, Esterified Estrogens

Appears to be metabolized partially by CYP3A4.106 107 108

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma estrogen concentrations).106 107 108

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased plasma estrogen concentrations).106 107 108

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Anticoagulants, oral

Possible decreased anticoagulant actionb

Monitor; increase warfarin dosage if requiredb

Antifungals, azoles (itraconazole, ketoconazole)

Possible increased plasma estrogen concentrations; increased potential for adverse effects106 107 108

Carbamazepine

Possible decreased plasma estrogen concentrations; potential for decrease in therapeutic effects and/or changes in uterine bleeding106 107 108

Corticosteroids (hydrocortisone)

Enhanced anti-inflammatory effects of hydrocortisone in patients with chronic inflammatory skin diseaseb

Observe for signs of excessive corticosteroid effects; adjust corticosteroid dosage when initiating or discontinuing estrogenb

Grapefruit juice

Possible increased plasma estrogen concentrations; increased potential for adverse effects106 107 108

Macrolide antibiotics (clarithromycin, erythromycin)

Possible increased plasma estrogen concentrations; increased potential for adverse effects106 107 108

Phenobarbital

Possible decreased plasma estrogen concentrations; potential for decrease in therapeutic effects and/or changes in uterine bleeding106 107 108

Rifampin

Possible decreased plasma estrogen concentrations; potential for decrease in therapeutic effects and/or changes in uterine bleeding106 107 108

Ritonavir

Possible increased plasma estrogen concentrations; increased potential for adverse effects106 107 108

St. John’s wort (Hypericum perforatum)

Possible decreased plasma estrogen concentrations; potential for decrease in therapeutic effects and/or changes in uterine bleeding106 107 108

Thyroid agents

Increased thyroid-binding globulin concentrations106 107 108

Increased dosages of thyroid replacement agents may be needed; monitor thyroid function106 107 108

Estropipate, Esterified Estrogens Pharmacokinetics

Absorption

Bioavailability

Estrogens are well absorbed from the GI tract.106 107 108

Distribution

Extent

Widely distributed;b highest concentrations found in sex hormone target organs.106 107 108

Plasma Protein Binding

50–80%.b

Elimination

Metabolism

Metabolized in the liver; the kidney, gonads, and muscle tissue involved to some extent.b Estrogens metabolized partially by CYP3A4.106 107 108

Extensive metabolic conversion (i.e., estradiol converted to estrone, both converted to estriol) takes place in the liver.106 107 108

Estrogens 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.106 107 108

Elimination Route

Estrogens and their metabolites are excreted mainly in urine.106 107 108

Actions

  • Estropipate is estrone solubilized as the sulfate and stabilized with piperazine.106

  • Esterified estrogens is a mixture of the sodium salts of the sulfate esters of the estrogenic substances excreted by pregnant mares.107

  • Exogenous estrogens elicit, to varying degrees, all the pharmacologic responses usually produced by endogenous estrogens.a

Advice to Patients

  • Importance of providing patient a copy of the manufacturer’s patient information.106 107 108

  • Risk of cancer of the uterus in postmenopausal women.106 107 108 Importance of reporting any unusual vaginal bleeding to clinicians.106 107 108

  • Risk of MI, stroke, breast cancer, and venous thromboembolism.106 107 108 Importance of not using estrogens to prevent heart disease, MI, or strokes.106 107 108

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.106 107 108

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.106 107 108

  • Importance of informing patients of other important precautionary information.106 107 108 (See Cautions.)

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