mestranol/norethindrone (Discontinued)

Brand and Other Names:Necon 1/50, Norinyl 1+50
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

mestranol/norethindrone

tablet

  • 50mcg/1mg

Oral Contraceptive

1 hormonally active tablet qDay for 21 days, THEN 1 inert tablet (or tablet-free) for 7 days, repeat cycle

Follow manufacturer's color-coding (active vs inert)

Start on Day 1 of menstrual cycle or Sunday following start of menses

Initiating after Pregnancy

Increased risk for venous thromboembolism following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days, but does not return to normal until 42 days after delivery

CDC guidelines recommend waiting 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)

Initiating after vaginal birth: Wait at least 3 weeks

Initiating after caesarean section birth: Wait at least 6 weeks

Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives

Renal Impairment

Use caution; monitor blood presssure

Hepatic Impairment

Do not administer

Safety and efficacy not established

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Interactions

Interaction Checker

and mestranol/norethindrone

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            Contraindicated (2)

            • mifepristone

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

            • tranexamic acid oral

              tranexamic acid oral, mestranol. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of tranexamic acid oral and combination hormonal contraceptives increases thrombotic risk .

            Serious - Use Alternative (66)

            • abametapir

              abametapir will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              abametapir will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • acitretin

              acitretin decreases effects of norethindrone by unknown mechanism. Contraindicated. Contraceptive failure may result.

            • amobarbital

              amobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • antithrombin alfa

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

            • antithrombin III

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

            • apalutamide

              apalutamide will decrease the level or effect of mestranol 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 norethindrone 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.

            • argatroban

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

            • bosentan

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

            • bemiparin

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

            • bivalirudin

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

            • brigatinib

              brigatinib will decrease the level or effect of mestranol 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.

              brigatinib will decrease the level or effect of norethindrone 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.

            • butabarbital

              butabarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • carbamazepine

              carbamazepine will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • butalbital

              butalbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • carbamazepine

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

              carbamazepine decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in loss of contraceptive efficacy.

            • cimetidine

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

            • clarithromycin

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

            • dalteparin

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

            • darunavir

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

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

            • efavirenz

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

            • elagolix

              mestranol decreases effects of elagolix by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Based on the mechanism of action of elagolix, estrogen-containing contraceptives are expected to reduce elagolix efficacy. Effects of progestin-only contraceptives on the efficacy of elagolix is unknown. Advise women to use nonhormonal contraceptives during treatment with elagolix and for 1 week after discontinuing elagolix.

            • enoxaparin

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

            • enzalutamide

              enzalutamide will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

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

            • erythromycin base

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

            • fosphenytoin

              fosphenytoin will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • ethotoin

              ethotoin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • fedratinib

              mestranol will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fondaparinux

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

            • fosphenytoin

              fosphenytoin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • heparin

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

            • idelalisib

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

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

            • ivosidenib

              ivosidenib will decrease the level or effect of mestranol 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.

              ivosidenib will decrease the level or effect of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              ivosidenib will decrease the level or effect of norethindrone 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.

            • ketoconazole

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

            • lesinurad

              lesinurad decreases effects of norethindrone 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.

            • lonafarnib

              mestranol will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • lopinavir

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

            • lorlatinib

              lorlatinib will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Monitor response to estrogens and progestins whenever a CYP3A4 inducer is added to or discontinued, and adjust hormone dosage as necessary. For adequate protection against conception, advise additional or alternative nonhormonal birth control during coadministration with CY3A4 inducers and beyond discontinuation of the CYP3A4 inducers for ~for 3 plasma half-lives.

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

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • mifepristone

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

            • mitotane

              mitotane will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • nefazodone

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

            • nevirapine

              nevirapine decreases levels of mestranol by unknown mechanism. Contraindicated.

            • pentobarbital

              pentobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • phenindione

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

            • phenobarbital

              phenobarbital will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

              phenobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • phenytoin

              phenytoin will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

              phenytoin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • primidone

              primidone will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

              primidone decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. Contraceptive failure may result.

            • protamine

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

            • rifabutin

              rifabutin will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • quinidine

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

            • rifabutin

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

              rifabutin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • rifampin

              rifampin decreases levels of norethindrone by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

              rifampin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

              rifampin will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use of nonhormonal contraceptives advised

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

            • rifapentine

              rifapentine will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

              rifapentine decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • saquinavir

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

            • sugammadex sodium

              sugammadex sodium decreases effects of norethindrone 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.

            • secobarbital

              secobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

            • St John's Wort

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

            • tipranavir

              tipranavir decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

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

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

            • topiramate

              topiramate will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • tucatinib

              tucatinib will increase the level or effect of mestranol 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

              tucatinib will increase the level or effect of norethindrone 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.

            • voxelotor

              voxelotor will increase the level or effect of norethindrone 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.

              voxelotor will increase the level or effect of mestranol 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.

            • warfarin

              mestranol decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            Monitor Closely (195)

            • albiglutide

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

            • alpelisib

              alpelisib will decrease the level or effect of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • amikacin

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

            • aminocaproic acid

              mestranol decreases effects of aminocaproic acid by pharmacodynamic antagonism. Use Caution/Monitor. Risk of thromboembolic disorder.

            • amiodarone

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

            • amobarbital

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

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

            • amoxicillin

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

            • atazanavir

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

            • ampicillin

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

            • apalutamide

              apalutamide will decrease the level or effect of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

            • aprepitant

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

            • armodafinil

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

            • artemether/lumefantrine

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

            • atazanavir

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

            • atorvastatin

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

            • avapritinib

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

            • axitinib

              mestranol increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azithromycin

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

            • budesonide

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

            • butabarbital

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

            • butalbital

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

            • cannabidiol

              cannabidiol will decrease the level or effect of mestranol by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • cefaclor

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

            • cefadroxil

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

            • cefprozil

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

            • ceftibuten

              ceftibuten will decrease the level or effect of mestranol 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 norethindrone 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 mestranol 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 mestranol 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 norethindrone 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.

            • chlorhexidine oral

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

            • clarithromycin

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

            • clindamycin

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

            • colesevelam

              colesevelam decreases levels of norethindrone by drug binding in GI tract. Use Caution/Monitor. Administer oral contraceptives containing norethindrone/ethinyl estradiol at least 4 hr before colesevelam to avoid decreased absorption.

            • conivaptan

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

            • cortisone

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

            • crofelemer

              crofelemer increases levels of norethindrone 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.

            • cyclosporine

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

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

              mestranol increases levels of cyclosporine by unknown mechanism. Use Caution/Monitor.

            • dabrafenib

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

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

            • dapsone

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

            • elagolix

              elagolix decreases levels of norethindrone 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.

            • darifenacin

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

            • darunavir

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

            • dasatinib

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

            • deferasirox

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

            • demeclocycline

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

            • DHEA, herbal

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

            • dicloxacillin

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

            • doxycycline

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

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

            • efavirenz

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

            • elagolix

              elagolix decreases levels of mestranol 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.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of mestranol 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.

              elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

            • encorafenib

              encorafenib, norethindrone. 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, mestranol. 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.

            • ertapenem

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

            • etravirine

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • eslicarbazepine acetate

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

            • ethotoin

              mestranol decreases effects of ethotoin by decreasing metabolism. Use Caution/Monitor.

            • etravirine

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

            • exenatide injectable solution

              mestranol, exenatide injectable solution. Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. The effect of exenatide to slow gastric emptying may reduce the extent and rate of oral medications that require rapid GI absorption. Advise patients to take oral contraceptives at least 1 hr before exenatide. .

            • exenatide injectable suspension

              mestranol, exenatide injectable suspension. Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. The effect of exenatide to slow gastric emptying may reduce the extent and rate of oral medications that require rapid GI absorption. Advise patients to take oral contraceptives at least 1 hr before exenatide.

            • fedratinib

              fedratinib will increase the level or effect of norethindrone 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 mestranol 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 mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir, norethindrone. unspecified interaction mechanism. Use Caution/Monitor. Variable effect on norethindrone. Use non-hormonal contraception.

            • finerenone

              mestranol will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fleroxacin

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

            • flibanserin

              mestranol will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • flucloxacillin

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

            • fludrocortisone

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

            • fosamprenavir

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

              fosamprenavir, mestranol. unspecified interaction mechanism. Use Caution/Monitor. Variable effect on estradiol. Use non-hormonal contraception.

            • fosfomycin

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

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

              mestranol decreases effects of fosphenytoin by decreasing metabolism. Use Caution/Monitor.

            • gemifloxacin

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

            • gentamicin

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

            • griseofulvin

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

            • hemin

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

            • hydrocortisone

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

            • iloperidone

              iloperidone increases levels of mestranol 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.

              iloperidone increases levels of norethindrone 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.

            • indinavir

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

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

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

            • insulin degludec

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

            • istradefylline

              istradefylline will increase the level or effect of mestranol 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.

            • insulin degludec/insulin aspart

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

            • insulin inhaled

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

            • istradefylline

              istradefylline will increase the level or effect of norethindrone 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 mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoconazole

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

            • lamotrigine

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

              norethindrone 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 mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • letermovir

              letermovir increases levels of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lemborexant

              mestranol will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • levofloxacin

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

            • linezolid

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

            • liraglutide

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

            • lixisenatide

              lixisenatide will decrease the level or effect of mestranol by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. Oral contraceptives should be taken at least 1 hr before lixisenatide administration or 11 hr after lixisenatide.

            • lomitapide

              mestranol increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lopinavir

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

            • loratadine

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

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, mestranol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

            • lumefantrine

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

            • maraviroc

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

              norethindrone 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 mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • metformin

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

            • meropenem

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

            • methylprednisolone

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

            • metronidazole

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

            • miconazole vaginal

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

            • midazolam intranasal

              mestranol will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • mifepristone

              mifepristone decreases effects of norethindrone by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.

              mifepristone decreases effects of mestranol by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.

            • minocycline

              minocycline will decrease the level or effect of mestranol 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of nonhormonal contraceptives advised while in therapy

            • mitotane

              mitotane decreases levels of mestranol 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.

            • modafinil

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

            • moxifloxacin

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

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

            • nefazodone

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

            • nelfinavir

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

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

              nelfinavir decreases levels of mestranol by increasing metabolism. Use Caution/Monitor. May result in contraceptive failure.

            • neomycin PO

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

            • ritonavir

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

            • nevirapine

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

            • nicardipine

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

            • nifedipine

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

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

            • nilotinib

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

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

            • nitisinone

              nitisinone will increase the level or effect of mestranol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

            • nitrofurantoin

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

            • oxytetracycline

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

            • phenobarbital

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

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

            • phenytoin

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

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

              mestranol decreases effects of phenytoin by decreasing metabolism. Use Caution/Monitor.

            • pivmecillinam

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

            • prednisone

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

            • primidone

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

            • quercetin

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

            • quinupristin/dalfopristin

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

            • ranolazine

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

            • ribociclib

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

            • rifampin

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

            • rifapentine

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

            • ritonavir

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

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

              ritonavir decreases levels of mestranol by increasing metabolism. Use Caution/Monitor. May result in contraceptive failure; use additional or alternative method.

            • romidepsin

              romidepsin decreases effects of mestranol by receptor binding competition. Use Caution/Monitor.

            • roxithromycin

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

            • rucaparib

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

            • rufinamide

              rufinamide decreases effects of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Rufinamide is a weak inducer of the CYP 3A4 enzyme and can decrease exposure of drugs that are substrates of CYP3A4. .

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

            • secobarbital

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

            • siltuximab

              siltuximab, norethindrone. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

            • selegiline transdermal

              mestranol increases levels of selegiline transdermal by Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives inhibit the N demethylatin of selegiline.

            • siltuximab

              siltuximab, mestranol. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

            • simvastatin

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

            • sirolimus

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

            • St John's Wort

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

            • stiripentol

              stiripentol, norethindrone. 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.

              stiripentol, mestranol. 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 mestranol 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sugammadex

              sugammadex decreases levels of mestranol by unspecified interaction mechanism. Use Caution/Monitor. Risk of contraceptive failure.

            • sulfadiazine

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

            • sulfamethoxypyridazine

              sulfamethoxypyridazine decreases effects of mestranol by unspecified interaction mechanism. Use Caution/Monitor.

            • sulfisoxazole

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

            • tazemetostat

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

              mestranol will increase 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 norethindrone 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 mestranol 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 mestranol 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use alternative contraception

            • temocillin

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

            • tetracycline

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

            • tinidazole

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

            • tobramycin

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

            • tolvaptan

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

            • topiramate

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

            • tranexamic acid injection

              tranexamic acid injection, mestranol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of thromboembolic disorder.

            • trazodone

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

            • trimethoprim

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

            • vancomycin

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

            • verapamil

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

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

            • voriconazole

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

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

            • zafirlukast

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

            Minor (44)

            • alfalfa

              alfalfa decreases effects of mestranol by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

            • amitriptyline

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

            • amoxapine

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

            • amphotericin B deoxycholate

              amphotericin B deoxycholate decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • androstenedione

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

            • aprepitant

              aprepitant decreases levels of mestranol by increasing metabolism. Minor/Significance Unknown.

            • boron

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

            • clomipramine

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

            • clotrimazole

              clotrimazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • cyanocobalamin

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

            • desipramine

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

            • dosulepin

              mestranol, 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

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

            • felbamate

              felbamate decreases levels of mestranol by unknown mechanism. Minor/Significance Unknown.

            • fluconazole

              fluconazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • folic acid

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

            • green tea

              mestranol increases levels of green tea by decreasing elimination. Minor/Significance Unknown. (Caffeine).

            • griseofulvin

              griseofulvin decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • imipramine

              mestranol, 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 mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketoconazole

              ketoconazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • L-methylfolate

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

            • lofepramine

              mestranol, 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

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

            • magnesium citrate

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

            • magnesium hydroxide

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

            • magnesium oxide

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

            • magnesium sulfate

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

            • maprotiline

              mestranol, 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

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

            • miconazole vaginal

              miconazole vaginal decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • mineral oil

              mineral oil decreases levels of mestranol by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • mycophenolate

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

            • naratriptan

              mestranol increases effects of naratriptan by unspecified interaction mechanism. Minor/Significance Unknown.

            • nortriptyline

              mestranol, 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 mestranol by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pioglitazone

              pioglitazone decreases levels of mestranol by unknown mechanism. Minor/Significance Unknown.

            • pleurisy root

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

            • posaconazole

              posaconazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

            • protriptyline

              mestranol, 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

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

            • pyridoxine (Antidote)

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

            • ribociclib

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

            • ropinirole

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

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            Adverse Effects

            Frequency Not Defined

            Common

            • Emotional lability
            • Headache
            • Breast symptoms
            • Menstrual cramps
            • Abdominal pains
            • Nausea

            Serious

            • Arterial/venous thromboembolism
            • Hypertension
            • MI
            • Cerebral hemorrhage
            • Gallbladder disease
            • Hepatic adenoma
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            Warnings

            Black Box Warnings

            Cigarette smoking & risk of cardiovascular disease

            • Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use
            • This risk increases w/ age (>35 yr) & with heavy smoking (15 or more cigarettes/day)
            • Advise women who use hormonal oral contraceptives not to smoke

            Contraindications

            Documented hypersensitivity

            Active or history of breast cancer

            Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease

            Estrogen-dependent neoplasia

            Liver disease, liver tumors

            Undiagnosed abnormal vaginal bleeding

            Uncontrolled hypertension

            Diabetes mellitus with vascular involvement

            Jaundice with prior oral contraceptive use

            Precautions

            Family history of breast cancer and or DVT/PE, current/history of depression, endometriosis, DM, HTN, bone mineral density changes, renal/hepatic impairment, bone metabolic disease, SLE; conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)

            Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery

            Discontinue 4 week before major surgery or prolonged immobilization

            Patients on warfarin, oral anticoagulants (increase in anticoagulant dose may be warranted)

            Some studies link OCP use with increased risk of breast cancer, whereas other studies have not shown a change in risk; woman's risk depends on conditions where naturally high hormone levels persist for long periods of time including early onset menstruation before age 12, late onset menopause, after age 55, first child after age 30, nulliparity

            Increased risk of cervical cancer with OCP use, however HPV remains as main risk factor for this cancer; evidence suggests long-term use of OCPs, 5 or more years, may be associated with increased risk

            Increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use

            CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease risk for venous thromboembolism before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum) should not use combined hormonal contraceptives (MMWR July 7, 2011)

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            Pregnancy & Lactation

            Pregnancy Category: X

            Lactation: small amounts of steroids are excreted in breast milk; estrogens may reduce quality/quantity of milk; may be prudent to use other forms of birth control until full weaning (AAP Committee states compatible w/ nursing)

            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

            Mestranol: Estrogen; reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increases synthesis of DNA, RNA, and various proteins in target tissues

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

            Absorption

            Bioavailability: 60% (norethindrone)

            Peak plasma time: 8 hr (ethinyl estradiol [active metabolite]); 1-2 hr (norethindrone)

            Distribution

            Protein bound: 80% (ethinyl estradiol [active metabolite]); 61% (norethindrone)

            Metabolism

            Mestranol: Metabolized to ethinyl estradiol via demethylation

            Norethindrone: Liver

            Metabolites

            • Mestranol metabolized to ethinyl estradiol; ethinyl estradiol further metabolized to estriol, estrone by liver CYP3A4
            • Norethindrone: Sulfate and glucuronide metabolites (inactive)

            Elimination

            Half-life: 4-13 hr (norethindrone)

            Excretion

            • Ethinyl estradiol (active metabolite): in urine as conjugates, most estrogens are also excreted in the bile and undergo enterohepatic recycling
            • Norethindrone: 33-81% urine; 35-43% feces
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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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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.