conjugated estrogens/medroxyprogesterone (Rx)

Brand and Other Names:Premphase, Prempro

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

conjugated estrogens/medroxyprogesterone

tablet

  • 0.3 mg/1.5mg
  • 0.45 mg/1.5mg
  • 0.625 mg/2.5mg
  • 0.625 mg/5mg
  • 0.625 mg/5mg plus conjugated estrogen 0.625 mg (Premphase)

Menopause

Indicated in women who have a uterus for the treatment of moderate-to-severe vasomotor symptoms or vulvar and vaginal atrophy associated with the menopause

Also indicated for prevention of postmenopausal osteoporosis; when prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and nonestrogen medications should be carefully considered

Premphase (biphasic regimen)

  • 1 pure estrogen tablet qDay Days 1-14, THEN
  • 1 combo tablet PO qDay on days 15-28 of cycle

Prempro

  • 1 tablet PO qDay

Not recommended

Next:

Interactions

Interaction Checker

and conjugated estrogens/medroxyprogesterone

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            Contraindicated (2)

            • fezolinetant

              conjugated estrogens will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • ospemifene

              ospemifene, conjugated estrogens. Either increases effects of the other by pharmacodynamic synergism. Contraindicated.

            Serious - Use Alternative (51)

            • acitretin

              acitretin decreases effects of medroxyprogesterone by unknown mechanism. Avoid or Use Alternate Drug. Contraceptive failure may result.

            • anastrozole

              conjugated estrogens decreases effects of anastrozole by pharmacodynamic antagonism. Contraindicated.

            • antithrombin alfa

              conjugated estrogens decreases effects of antithrombin alfa by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • antithrombin III

              conjugated estrogens decreases effects of antithrombin III by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • apalutamide

              apalutamide will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              apalutamide will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • argatroban

              conjugated estrogens decreases effects of argatroban by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • brigatinib

              brigatinib will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration of hormonal contraceptives with brigatinib can result in decreased concentrations and loss of efficacy. Brigatinib can cause fetal harm. Women should use an effective nonhormonal method of contraception during treatment and for at least 4 months after the last brigatinib dose.

            • bemiparin

              conjugated estrogens decreases effects of bemiparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • bivalirudin

              conjugated estrogens decreases effects of bivalirudin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • carbamazepine

              carbamazepine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dabrafenib

              dabrafenib will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dalteparin

              conjugated estrogens decreases effects of dalteparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • darunavir

              darunavir will decrease the level or effect of conjugated estrogens by unspecified interaction mechanism. Avoid or Use Alternate Drug.

              darunavir will decrease the level or effect of medroxyprogesterone by unspecified interaction mechanism. Avoid or Use Alternate Drug. Oral formulation only

            • enoxaparin

              conjugated estrogens decreases effects of enoxaparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • etrasimod

              etrasimod, medroxyprogesterone. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.

            • enzalutamide

              enzalutamide will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin base

              erythromycin base will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              fexinidazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fondaparinux

              conjugated estrogens decreases effects of fondaparinux by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • idelalisib

              idelalisib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • givosiran

              givosiran will increase the level or effect of conjugated estrogens by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

            • heparin

              conjugated estrogens decreases effects of heparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • idelalisib

              idelalisib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • itraconazole

              itraconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lesinurad

              lesinurad decreases effects of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use additional methods of nonhormonal contraception. Do not rely on hormonal contraception alone when taking lesinurad.

            • lorlatinib

              lorlatinib will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              lorlatinib will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mavacamten

              mavacamten will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • mitotane

              mitotane will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mifepristone

              mifepristone will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nefazodone

              nefazodone will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nelfinavir

              nelfinavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pacritinib

              medroxyprogesterone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              conjugated estrogens will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenindione

              conjugated estrogens decreases effects of phenindione by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • ribociclib

              ribociclib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • protamine

              conjugated estrogens decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • quinidine

              quinidine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • rifabutin

              rifabutin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sugammadex sodium

              sugammadex sodium decreases effects of medroxyprogesterone by receptor binding competition. Avoid or Use Alternate Drug. In vitro binding studies showed that sugammadex may bind to progestogen, thereby decreasing progestogen exposure. Therefore, a sugammadex bolus dose is considered to be equivalent to missing dose(s) of hormonal contraceptives containing an estrogen or progestogen. If an oral contraceptive is taken on the same day of sugammadex, or the patient has a transdermal or implant hormonal contraceptive, the patient must use an additional, nonhormonal contraceptive method or back-up method of contraception (eg, condoms and spermicides) for the next 7 days.

            • tucatinib

              tucatinib will increase the level or effect of conjugated estrogens 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.

              tucatinib will increase the level or effect of medroxyprogesterone 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.

            • voriconazole

              voriconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of medroxyprogesterone 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.

            Monitor Closely (188)

            • albiglutide

              medroxyprogesterone decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Medroxyprogesterone may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              conjugated estrogens decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

            • ambrisentan

              ambrisentan will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ambrisentan will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amikacin

              amikacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • amiodarone

              amiodarone will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aprepitant

              aprepitant will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • armodafinil

              armodafinil will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

              armodafinil will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atazanavir

              atazanavir, medroxyprogesterone. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.

            • atazanavir

              atazanavir, conjugated estrogens. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated . Use alternatives if available.

            • atogepant

              conjugated estrogens will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atorvastatin

              atorvastatin will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • axitinib

              conjugated estrogens decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azithromycin

              azithromycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

            • aztreonam

              aztreonam will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              bosentan will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • budesonide

              budesonide will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • butabarbital

              butabarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cannabidiol

              cannabidiol, conjugated estrogens. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • cefadroxil

              cefadroxil will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • cefamandole

              cefamandole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • cefpirome

              cefpirome will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              cenobamate will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • cephalexin

              cephalexin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ceritinib

              ceritinib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ceritinib

              ceritinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlorhexidine oral

              chlorhexidine oral will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ciprofloxacin

              ciprofloxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              clarithromycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

              clarithromycin will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clindamycin

              clindamycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • clobazam

              clobazam will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clobazam is a weak CYP3A4 inducer; effectiveness of hormonal contraceptives may be diminished when given concurrently with clobazam. Additional non-hormonal forms of contraception are recommended.

            • clotrimazole

              clotrimazole will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

              cortisone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crofelemer

              crofelemer increases levels of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

              crofelemer increases levels of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 and transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclosporine

              cyclosporine will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              cyclosporine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              cyclosporine will increase the level or effect of conjugated estrogens by Other (see comment). Use Caution/Monitor. may increase plasma concentrations of organic anion transporter protein substrates

            • dabrafenib

              dabrafenib will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dapsone

              dapsone will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • darifenacin

              darifenacin will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              dasatinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • demeclocycline

              demeclocycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • dexamethasone

              dexamethasone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              dexamethasone will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • doxycycline

              doxycycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              dronedarone will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix decreases levels of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eluxadoline

              eluxadoline increases levels of conjugated estrogens by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, conjugated estrogens. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              encorafenib, medroxyprogesterone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enzalutamide

              enzalutamide will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • ertapenem

              ertapenem will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • erythromycin base

              erythromycin base will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

              erythromycin base will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

              erythromycin ethylsuccinate will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

              erythromycin lactobionate will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

              erythromycin stearate will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              eslicarbazepine acetate will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptive failure possible. Use alternative if available.

            • etravirine

              etravirine will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

              etravirine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • exenatide injectable solution

              medroxyprogesterone decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Montior for glycemic control in diabetic patients.

              conjugated estrogens decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

            • exenatide injectable suspension

              medroxyprogesterone decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

              conjugated estrogens decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

            • fedratinib

              fedratinib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • felodipine

              felodipine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fleroxacin

              fleroxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • fluconazole

              fluconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosaprepitant

              fosaprepitant will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosfomycin

              fosfomycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              fosphenytoin will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              fosphenytoin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • gemifloxacin

              gemifloxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternative if available.

            • gentamicin

              gentamicin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • griseofulvin

              griseofulvin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hemin

              conjugated estrogens decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

            • hyaluronidase

              conjugated estrogens decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • iloperidone

              iloperidone increases levels of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

              imatinib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              indinavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              indinavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • insulin degludec

              medroxyprogesterone decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              conjugated estrogens decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

            • insulin degludec/insulin aspart

              conjugated estrogens decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              medroxyprogesterone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

            • insulin inhaled

              medroxyprogesterone decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              conjugated estrogens decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

            • isavuconazonium sulfate

              conjugated estrogens will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ivosidenib

              ivosidenib will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ketoconazole will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              ketoconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lamotrigine

              conjugated estrogens decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.

              medroxyprogesterone will decrease the level or effect of lamotrigine by increasing hepatic clearance. Use Caution/Monitor. Combination oral contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation.

            • lapatinib

              lapatinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              lapatinib will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lenacapavir

              lenacapavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lenacapavir

              lenacapavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • levofloxacin

              levofloxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • levoketoconazole

              levoketoconazole will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              levoketoconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              levoketoconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • linezolid

              linezolid will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • liraglutide

              medroxyprogesterone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Medroxyprogesterone may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

            • liraglutide

              conjugated estrogens decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.

            • lonapegsomatropin

              conjugated estrogens will decrease the level or effect of lonapegsomatropin by Other (see comment). Use Caution/Monitor. Oral estrogens may reduce serum insulin-like growth factor-1 response to lonapegsomatropin. Patients receiving oral estrogen replacement may require higher lonapegsomatropin dosages.

            • lopinavir

              lopinavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              lopinavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loratadine

              loratadine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • lovastatin

              lovastatin will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lumefantrine

              lumefantrine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • maraviroc

              conjugated estrogens increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • marijuana

              marijuana will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • meropenem

              meropenem will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • meropenem/vaborbactam

              meropenem/vaborbactam will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • metformin

              conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

              medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of medroxyprogesterone 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.

            • metronidazole

              metronidazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • minocycline

              minocycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • moxifloxacin

              moxifloxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • nafcillin

              nafcillin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • nefazodone

              nefazodone will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nefazodone will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nelfinavir

              nelfinavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • neomycin PO

              neomycin PO will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              nicardipine will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternative if available.

              nicardipine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nifedipine

              nifedipine will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nifedipine will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • nilotinib

              nilotinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nilotinib will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nitrofurantoin

              nitrofurantoin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ofloxacin

              ofloxacin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxytetracycline

              oxytetracycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • paromomycin

              paromomycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • pentobarbital

              pentobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • phenobarbital

              phenobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

              phenobarbital will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur.

              phenytoin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenytoin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • pivmecillinam

              pivmecillinam will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternative if available.

            • posaconazole

              posaconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prednisone

              prednisone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pretomanid

              pretomanid will increase the level or effect of conjugated estrogens by Other (see comment). Modify Therapy/Monitor Closely. In vitro studies demonstrated that pretomanid significantly inhibits OAT3; monitor for increased adverse effects and consider dosage reduction for OAT3 substrates.

            • primidone

              primidone will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              primidone will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • quercetin

              quercetin will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quinidine

              quinidine will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternative if available.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              quinupristin/dalfopristin will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ribociclib

              ribociclib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

            • rifampin

              rifampin will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              rifampin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • rifapentine

              rifapentine will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifapentine will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • ritonavir

              ritonavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ritonavir will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • roxithromycin

              roxithromycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.

            • rufinamide

              rufinamide will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

              saquinavir will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              secobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • simvastatin

              simvastatin will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • St John's Wort

              St John's Wort will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

            • siponimod

              siponimod and medroxyprogesterone 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.

            • sirolimus

              sirolimus will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • somapacitan

              conjugated estrogens 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 Wort

              St John's Wort will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, conjugated estrogens. 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, medroxyprogesterone. 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.

            • streptomycin

              streptomycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sulfadiazine

              sulfadiazine will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • sulfamethoxazole

              sulfamethoxazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • sulfisoxazole

              sulfisoxazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tacrolimus

              tacrolimus will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tazemetostat

              conjugated estrogens will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              tecovirimat will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • teicoplanin

              teicoplanin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tesamorelin

              tesamorelin will decrease the level or effect of medroxyprogesterone by altering metabolism. Use Caution/Monitor. Use alternative contraception

            • temocillin

              temocillin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tenapanor

              tenapanor decreases levels of conjugated estrogens by Other (see comment). Use Caution/Monitor. Comment: Tenapanor (an inhibitor of intestinal uptake transporter, OATP2B1) may reduce the exposure of OATP2B1 substrates.

            • teniposide

              teniposide will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tesamorelin

              tesamorelin will decrease the level or effect of conjugated estrogens by altering metabolism. Use Caution/Monitor. May decrease efficacy; monitor

            • tetracycline

              tetracycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ticarcillin

              ticarcillin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tigecycline

              tigecycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternative if available.

            • tobramycin

              tobramycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            Minor (42)

            • acetazolamide

              acetazolamide will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              acetazolamide will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amitriptyline

              conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • anastrozole

              anastrozole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amoxapine

              conjugated estrogens, amoxapine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • anastrozole

              anastrozole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • androstenedione

              androstenedione increases effects of conjugated estrogens by pharmacodynamic synergism. Minor/Significance Unknown.

            • ascorbic acid

              conjugated estrogens decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

            • boron

              boron increases levels of conjugated estrogens by altering metabolism. Minor/Significance Unknown.

            • clomipramine

              conjugated estrogens, clomipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • cyanocobalamin

              conjugated estrogens decreases levels of cyanocobalamin by altering metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              cyclophosphamide will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desipramine

              conjugated estrogens, desipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • larotrectinib

              larotrectinib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dosulepin

              conjugated estrogens, dosulepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • doxepin

              conjugated estrogens, doxepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • exemestane

              conjugated estrogens decreases levels of exemestane by increasing metabolism. Minor/Significance Unknown.

            • folic acid

              conjugated estrogens decreases levels of folic acid by altering metabolism. Minor/Significance Unknown.

            • imipramine

              conjugated estrogens, imipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • isoniazid

              isoniazid will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • L-methylfolate

              conjugated estrogens decreases levels of L-methylfolate by altering metabolism. Minor/Significance Unknown.

            • larotrectinib

              larotrectinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lofepramine

              conjugated estrogens, lofepramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • magnesium chloride

              conjugated estrogens decreases levels of magnesium chloride by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.

            • magnesium citrate

              conjugated estrogens decreases levels of magnesium citrate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.

            • magnesium hydroxide

              conjugated estrogens decreases levels of magnesium hydroxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.

            • magnesium oxide

              conjugated estrogens decreases levels of magnesium oxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.

            • magnesium sulfate

              conjugated estrogens decreases levels of magnesium sulfate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.

            • maitake

              maitake increases effects of medroxyprogesterone by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).

            • maprotiline

              conjugated estrogens, maprotiline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • metyrapone

              conjugated estrogens decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

            • mycophenolate

              mycophenolate decreases effects of conjugated estrogens by unknown mechanism. Minor/Significance Unknown. Clinical significance unclear.

            • nortriptyline

              conjugated estrogens, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • phytoestrogens

              phytoestrogens decreases effects of conjugated estrogens by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of conjugated estrogens by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • progesterone, natural

              progesterone, natural, conjugated estrogens. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Combination may produce breast tenderness.

            • protriptyline

              conjugated estrogens, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • pyridoxine

              conjugated estrogens decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.

            • pyridoxine (Antidote)

              conjugated estrogens decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.

            • ropinirole

              conjugated estrogens increases levels of ropinirole by unspecified interaction mechanism. Minor/Significance Unknown.

            • rose hips

              conjugated estrogens decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

            • taurine

              medroxyprogesterone decreases levels of taurine by unspecified interaction mechanism. Minor/Significance Unknown.

            • trazodone

              conjugated estrogens, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

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            Adverse Effects

            >10%

            Abdominal pain

            Breast enlargement

            Breast tenderness

            Bloating

            Nausea/vomiting

            Peripheral edema

            Frequency Not Defined

            Amenorrhea

            Breakthrough bleeding

            Depression

            Headache

            Melasma

            Spotting

            Weight changes

            Postmarketing Reports

            Ischemic colitis

            Growth potentiation of benign meningioma

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            Warnings

            Estrogen Plus Progestin Therapy

            Cardiovascular disorders and probable dementia

            • Estrogen plus progestin therapy should not be used for prevention of cardiovascular disease or dementia
            • The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo
            • The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo; it is unknown whether this finding applies to younger postmenopausal women

            Breast Cancer

            • The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer
            • 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
            • 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

            Estrogen-Alone Therapy

            Endometrial cancer

            • There is an increased risk of endometrial cancer in woman with a uterus who uses unopposed estrogens; adding progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer; adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding

            Cardiovascular disorders and probable dementia

            • Estrogen-alone therapy should not be used for prevention of cardiovascular disease or dementia
            • The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo
            • The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo
            • It is unknown whether this finding applies to younger postmenopausal women
            • In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens
            • Estrogens with or without progestins should be prescribed at lowest effective doses and for shortest duration consistent with treatment goals and risks for the individual woman

            Contraindications

            Undiagnosed abnormal genital bleeding

            Known, suspected, or history of breast cancer

            Known or suspected estrogen-dependent neoplasiaActive DVT, PE, or a history of these conditions

            Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions

            Known anaphylactic reaction or angioedema to PREMPRO/PREMPHASE

            Known liver dysfunction or disease

            Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

            Known or suspected pregnancy

            Cautions

            An increased risk of PE, DVT, stroke and MI reported with estrogen plus progestin therapy; an increased risk of stroke and DVT reported with estrogen-alone therapy;should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately

            Use caution in patients with bone mineral density changes, current/history of depression, diabetes mellitus, HTN, hyperlipidemia, hypertriglyceridemia, obesity, endometriosis, family history of breast cancer and/or DVT/PE, smoking, severe hypocalcemia

            If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery or prolonged immobilization or there are any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression

            Retinal vascular thrombosis reported in patients receiving estrogens; discontinue medication 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 discontinued

            Increased risk of post-op thromboembolic complications, MI, stroke, pulmonary emboli, DVT, Alzheimer's disease, cardiovascular disorders, probable dementia, and endometrial cancer

            Increased risk of endometrial cancer reported with use of unopposed estrogen therapy in a woman with a uterus; the reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users and appears dependent on duration of treatment and on estrogen dose

            Manage appropriately risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (eg, personal history or family history of VTE, obesity, and systemic lupus erythematosus)

            Use caution in patients with conditions exacerbated by fluid retention (eg, asthma, migraine, cardiac/renal dysfunction, epilepsy)

            Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions

            Patients on warfarin/oral anticoagulants: estrogens increase thromboembolic risk; increase in anticoagulant dose may be warranted

            Angioedema involving the tongue, larynx, face, hands, and feet requiring medical intervention has occurred postmarketing in patients taking this therapy; if angioedema involves the tongue, glottis, or larynx, airway obstruction may occur; patients who develop an anaphylactic reaction with or without angioedema after treatment should permanently discontinue therapy

            Not for use with conditions that predispose to hyperkalemia

            Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases; if hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce serum calcium level

            Increased risk of ovarian cancer reported in women who used hormonal therapy for menopausal symptoms

            Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important; adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding

            A 2 to 4-fold increase in risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens reported

            There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance

            In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications

            Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue medication

            Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range

            All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations; in addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results

            Studies of addition of a progestin for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone; endometrial hyperplasia may be a precursor to endometrial cancer; there are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens; these include an increased risk of breast cancer

            The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation

            There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose; adding a progestin to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer

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            Pregnancy & Lactation

            Pregnancy

            This drug combination should not be used during pregnancy; there appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy

            Lactation

            This drug combination should not be used during lactation; estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk

            Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving these drugs; caution should be exercised when this drug combination is administered to a nursing woman

            Pregnancy 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.

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            Pharmacology

            Mechanism of Action

            Estradiol: Endogenous estrogen; 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

            Medroxyprogestin: Progestin; inhibits secretion of gonadotropins from pituitary gland; prevents follicular maturation and ovulation, stimulates growth of mammary tissues

            Absorption

            Bioavailability: Readily absorbed from GI tract (conjugated estrogens)

            Onset: 2-4 wk (conjugated estrogens)

            Peak Plasma: 8 hr (conjugated estrogens)

            Distribution

            Protein Bound: 80% (conjugated estrogens); 90% (medroxyprogesterone)

            Metabolism

            Conjugated estrogens metabolized in liver to inactive sulfates and glucuronides

            Medroxyprogesterone metabolized in liver

            Metabolites: Estradiol, estrone, estriol (conjugated estrogens)

            Elimination

            Excretion (conjugated estrogens): Urine, most estrogens are also excreted in bile and undergo enterohepatic recycling

            Excretion (medroxyprogesterone): Urine

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            Patient Handout

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            Formulary

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            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.
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            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.