hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.simvastatinMonitor Closely (1)simvastatin will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.sirolimusMonitor Closely (1)sirolimus will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.somapacitanMonitor Closely (1)estropipate 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 estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.stiripentolMonitor Closely (2)stiripentol, estropipate. 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. stiripentol, estropipate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.streptomycinMonitor Closely (1)streptomycin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfadiazineMonitor Closely (1)sulfadiazine will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfamethoxazoleMonitor Closely (1)sulfamethoxazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfisoxazoleMonitor Closely (1)sulfisoxazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tacrolimusMonitor Closely (1)tacrolimus will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.teicoplaninMonitor Closely (1)teicoplanin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.temocillinMonitor Closely (1)temocillin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.teriflunomideMonitor Closely (1)teriflunomide decreases levels of estropipate by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tetracyclineMonitor Closely (1)tetracycline will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.ticarcillinMonitor Closely (1)ticarcillin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tigecyclineMonitor Closely (1)tigecycline will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tobramycinMonitor Closely (1)tobramycin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tolvaptanMonitor Closely (1)tolvaptan will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.trazodoneMonitor Closely (1)trazodone will decrease the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)estropipate, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.trimethoprimMonitor Closely (1)trimethoprim will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.trimipramineMinor (1)estropipate, trimipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of estropipate 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.vancomycinMonitor Closely (1)vancomycin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.verapamilMonitor Closely (2)verapamil will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. verapamil will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of estropipate 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 estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Frequency Not Defined Peripheral edema Depression Headache Melasma Bloating Nausea & vomiting Breast enlargement & tenderness 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 yr) during 5.6 yr of treatment with daily PO conjugated estrogens (CE 0.625 mg) combined with 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 yr 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 w/ daily CE 0.625 mg combined with 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 and dosage forms of estrogens and progestins Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with 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 Undiagnosed abnormal vaginal bleeding Uncontrolled hypertension Diabetes mellitus with vascular involvement Jaundice with prior oral contraceptive use Cautions Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, elderly, hepatic/renal impairment, uterine leiomyomata, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, ovarian cancer, exacerbation of endometriosis or other conditions, smoking and >35 years old, SLE, depression Fluid retention may exacerbate asthma, epilepsy, migraines, & cardiac or renal dysfunction 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. Hypercalcemia may occur in patients with breast cancer and bone metastases Increased risk of endometrial and ovarian cancer in postmenopausal women Long-term postmenopausal estrogen treatment has been associated with increased risk of breast cancer, MI, stroke, DVT, PE, and dementia May increase risk of thromboembolic disorders, may need to increase anticoagulant dose when administering concomitantly with anticoagulants 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 Semisynthetic conjugate of estrone with piperazine; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of LH and FSH from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues Pharmacokinetics Half-Life: IM: 1.5-5 hr Bioavailability: Readily absorbed through GI tract, skin, mucous membrane Protein bound: 50-80% Metabolism: Undergoes rapid and extensive first-pass metabolism in liver 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 No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. QL Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. ST Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. Plans Select State: Alabama