storage.magnesium hydroxideMinor (1)estrogens esterified decreases levels of magnesium hydroxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.magnesium oxideMinor (1)estrogens esterified decreases levels of magnesium oxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.magnesium sulfateMinor (1)estrogens esterified decreases levels of magnesium sulfate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.maprotilineMinor (1)estrogens esterified, maprotiline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.maravirocMonitor Closely (1)estrogens esterified increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .meropenem/vaborbactamMonitor Closely (1)meropenem/vaborbactam will decrease the level or effect of estrogens esterified by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.metyraponeMinor (1)estrogens esterified decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown. A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. It is generally advisable to discontinue estrogens prior to and during metyrapone administration.miconazole vaginalMonitor Closely (1)miconazole vaginal will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mifepristoneMonitor Closely (1)mifepristone will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mitotaneMonitor Closely (1)mitotane decreases levels of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.mycophenolateMinor (1)mycophenolate decreases effects of estrogens esterified by unknown mechanism. Minor/Significance Unknown. Clinical significance unclear.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nelfinavirMonitor Closely (1)nelfinavir will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nortriptylineMinor (1)estrogens esterified, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.ospemifeneContraindicated (1)ospemifene, estrogens esterified. Either increases effects of the other by pharmacodynamic synergism. Contraindicated.oxcarbazepineMonitor Closely (1)oxcarbazepine will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.pentobarbitalMonitor Closely (1)pentobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.phenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.phenytoinMonitor Closely (1)phenytoin will decrease the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. phytoestrogensMinor (1)phytoestrogens decreases effects of estrogens esterified by pharmacodynamic antagonism. Minor/Significance Unknown.pleurisy rootMinor (1)pleurisy root decreases effects of estrogens esterified by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.posaconazoleMonitor Closely (1)posaconazole will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.primidoneMonitor Closely (1)primidone will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.protriptylineMinor (1)estrogens esterified, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.pyridoxineMinor (1)estrogens esterified decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.pyridoxine (Antidote)Minor (1)estrogens esterified decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.quinidineMonitor Closely (1)quinidine will increase the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.quinupristin/dalfopristinMonitor Closely (1)quinupristin/dalfopristin will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifampinMonitor Closely (1)rifampin will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ritonavirMonitor Closely (1)ritonavir will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rose hipsMinor (1)estrogens esterified decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.siponimodMonitor Closely (1)siponimod and estrogens esterified both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.somapacitanMonitor Closely (1)estrogens esterified decreases effects of somapacitan by Other (see comment). Modify Therapy/Monitor Closely. Comment: Oral estrogens may reduce the serum IGF-1 response to somapacitan. Patients may require higher somapacitan dosages. See drug monograph for starting dose recommendations.St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.stiripentolMonitor Closely (1)stiripentol, estrogens esterified. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.tacrolimusMonitor Closely (1)tacrolimus will increase the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.teriflunomideMonitor Closely (1)teriflunomide decreases levels of estrogens esterified by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tolvaptanMonitor Closely (1)tolvaptan will increase the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Topiramate may compromise the efficacy of estrogens used for contraception or hormone replacement therapiestrazodoneMinor (1)estrogens esterified, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.trimipramineMinor (1)estrogens esterified, trimipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valproic acidMonitor Closely (1)estrogens esterified will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequencyverapamilMonitor Closely (1)verapamil will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Frequency Not Defined Common Edema, peripheral edema Headache Melasma Breast enlargement, breast tenderness Bloating Nausea Vomiting Less common Depression Amenorrhea Breakthrough bleeding Spotting Weight changes Corneal curvation change Black Box Warnings Estrogens increase risk of endometrial cancer Close clinical surveillance of all women taking estrogens is important Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring 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 Cardiovascular risks Estrogens with and without progestins should not be used to prevent cardiovascular disease Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 year) during 5.6 yr of treatment w/ daily PO conjugated estrogens (CE 0.625 mg) combined w/ medroxyprogesterone acetate (MPA 2.5 mg) compared with placebo Estrogens alone: A substudy of the WHI Study reported increased risk for stroke and DVT in postmenopausal women (aged 50-79 yr) during 6.8 year of treatment with oral conjugated estrogens (0.625 mg/day) alone compared with placebo Dementia risks Estrogens with and without progestins should not be used to prevent dementia Women's Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 4 yr of treatment with daily CE 0.625 mg combined w/ MPA 2.5 mg, compared with placebo Estrogens alone: A substudy of the WHIMS reported an increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 5.2 yr of treatment with conjugated estrogens 0.625 mg alone compared with placebo Unknown whether these findings apply to younger postmenopausal women Dose & duration In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations & dosage forms of estrogens & progestins Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose & for shortest duration consistent w/ treatment goals and individual risks Contraindications Documented hypersensitivity Active or history of breast cancer Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease Estrogen-dependent neoplasia, liver disease, liver tumors Uncontrolled hypertension Diabetes mellitus with vascular involvement Jaundice with prior oral contraceptive use Undiagnosed abnormal genital bleeding Cautions Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, liver impairment, uterine leiomyomata, smoking, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, hypothyroidism, ovarian cancer, exacerbation of endometriosis or other conditions Conditions exacerbated by fluid retention (asthma, epilepsy, migraine etc) Hypercalcemia may occur in patients with breast cancer and bone metastases Long-term postmenopausal estrogen treatment has been associated with an increased risk of breast cancer, MI, stroke, DVT, PE, and dementia Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery Concomitant warfarin, oral anticoagulants: estrogens increase risk of thromboembolic disorders; may need to increase anticoagulant dose Pregnancy Category: X Lactation: Controversial; estrogens are excreted into breast milk in small quantities, use cautionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Mixture of sodium salts and sulfate esters of estrogenic substances, principally estrone sodium sulfate; reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increase synthesis of DNA, RNA, and various proteins in target tissues Pharmacokinetics Protein Bound: 50-80% Metabolism: Principally and rapidly in liver and undergoes extensive first-pass metabolism to less active products such as estriol; kidneys, gonads, and muscle tissues may be involved in metabolism to some extent Metabolites: Estriol Excretion: Mainly in urine as conjugates with small amount of unchanged drug, most estrogens are also excreted in bile and undergo enterohepatic recycling BRAND FORM. UNIT PRICE PILL IMAGE Menest oral- 2.5 mg tabletMenest oral- 1.25 mg tabletMenest oral- 0.625 mg tabletMenest oral- 0.3 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationesterified estrogens oral