increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ribociclibribociclib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.schisandraschisandra will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.sertralinesertraline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.tetracyclinetetracycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.verapamilverapamil will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.abametapirMonitor Closely (1)estradiol vaginal will increase the level or effect of abametapir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.amiodaroneMinor (1)amiodarone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.amobarbitalMonitor Closely (1)amobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.apalutamideMonitor Closely (1)apalutamide will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.aprepitantMinor (1)aprepitant will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.atazanavirMonitor Closely (1)atazanavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.bicalutamideMinor (1)bicalutamide will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.bosentanMonitor Closely (1)bosentan will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.butabarbitalMonitor Closely (1)butabarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.butalbitalMonitor Closely (1)butalbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.carbamazepineMonitor Closely (1)carbamazepine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ceritinibMinor (1)ceritinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.clarithromycinMonitor Closely (1)clarithromycin will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.clotrimazoleMinor (1)clotrimazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cobicistatMonitor Closely (1)cobicistat will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.conivaptanMonitor Closely (1)conivaptan will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.crizotinibMinor (1)crizotinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclosporineMinor (1)cyclosporine will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dabrafenibMonitor Closely (1)dabrafenib will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.darunavirMonitor Closely (1)darunavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.dexamethasoneMonitor Closely (1)dexamethasone will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.diltiazemMinor (1)diltiazem will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.doxycyclineMinor (1)doxycycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dronedaroneMinor (1)dronedarone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.efavirenzMonitor Closely (1)efavirenz will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.enzalutamideMonitor Closely (1)enzalutamide will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin baseMinor (1)erythromycin base will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.erythromycin ethylsuccinateMinor (1)erythromycin ethylsuccinate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.erythromycin lactobionateMinor (1)erythromycin lactobionate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.erythromycin stearateMinor (1)erythromycin stearate will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.eslicarbazepine acetateMonitor Closely (1)eslicarbazepine acetate will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.etravirineMonitor Closely (1)etravirine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fluconazoleMinor (1)fluconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosamprenavirMonitor Closely (1)fosamprenavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.fosaprepitantMinor (1)fosaprepitant will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosphenytoinMonitor Closely (1)fosphenytoin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.grapefruitMonitor Closely (1)grapefruit will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.haloperidolMinor (1)haloperidol will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.idelalisibMonitor Closely (1)idelalisib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.iloperidoneMinor (1)iloperidone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.imatinibMonitor Closely (1)imatinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.indinavirMonitor Closely (1)indinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.itraconazoleMonitor Closely (1)itraconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.ketoconazoleMonitor Closely (1)ketoconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.lapatinibMinor (1)lapatinib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.levoketoconazoleMonitor Closely (2)levoketoconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities. estradiol vaginal will increase the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.lopinavirMonitor Closely (1)lopinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.lumacaftor/ivacaftorMonitor Closely (1)lumacaftor/ivacaftor will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.metronidazoleMinor (1)metronidazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.mitotaneMonitor Closely (1)mitotane will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.nelfinavirMonitor Closely (1)nelfinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.netupitant/palonosetronMinor (1)netupitant/palonosetron will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nicardipineMonitor Closely (1)nicardipine will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.oxcarbazepineMonitor Closely (1)oxcarbazepine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.pentobarbitalMonitor Closely (1)pentobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.phenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.phenytoinMonitor Closely (1)phenytoin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.posaconazoleMonitor Closely (1)posaconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.primidoneMonitor Closely (1)primidone will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.quinupristin/dalfopristinMinor (1)quinupristin/dalfopristin will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ribociclibMinor (1)ribociclib will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifampinMonitor Closely (1)rifampin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ritonavirMonitor Closely (1)ritonavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.saquinavirMonitor Closely (1)saquinavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.schisandraMinor (1)schisandra will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.sertralineMinor (1)sertraline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.somapacitanMonitor Closely (1)estradiol vaginal decreases effects of somapacitan by Other (see comment). Modify Therapy/Monitor Closely. Comment: Oral estrogens may reduce the serum IGF-1 response to somapacitan. Patients may require higher somapacitan dosages. See drug monograph for starting dose recommendations.St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tetracyclineMinor (1)tetracycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.verapamilMinor (1)verapamil will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities. >10% Headache (5-16%) 1-10% Vulvovaginal mycotic infection (5-8%) Vulvovaginal pruritus (8%) Back pain (7%) Abdominal pain (7%) Diarrhea (5%) Postmarketing Reports Causality not confirmed Reproductive system and breast disorders: Breast cancer, endometrial cancer, endometrial hyperplasia, vulvovaginal burning sensation, vulvovaginal pain, vaginismus, vaginal ulceration, genital pruritus, vulvovaginal rash, vulvovaginal swelling Cardiovascular: Deep vein thrombosis Gastrointestinal: Diarrhea Skin and subcutaneous tissue disorders: Rash, rash erythematous, rash pruritic urticaria Central nervous system: Aggravated migraine, depression, insomnia Miscellaneous: Fluid retention, weight increase, drug ineffectiveness, hypersensitivity, blood estrogen increase Immune system disorders: Hypersensitivity Metabolism and nutrition disorders: Fluid retention Psychiatric disorders: Depression, insomnia Genitourinary system: Vaginal discharge Black Box Warnings Increased risk of endometrial cancer Close clinical surveillance of all women taking estrogens is important Risk of