norgestrel/ethinyl estradiol (Rx)

Brand and Other Names:Cryselle, Low-Ogestrel, more...Elinest, Ogestrel
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

norgestrel/ethinyl estradiol

tablet

  • 0.3mg/30mcg (Cryselle, Elinest, Lo-Ogestrel, Lo/Ovral)
  • 0.5mg/50mcg (Ogestrel)

Contraception

Follow Manufacturer's color-coding for active versus inert tabs

Start on day 1 of menstrual cycle or Sunday following start of cycle

1 hormonally active tablet PO for 21 days, then 7 tablet-free days (or inert tablets as supplied); repeat cycle

Initiating after Pregnancy

Increased risk for venous thromboembolism (VTE) 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 pressure

Hepatic Impairment

Do not administer

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and norgestrel/ethinyl estradiol

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            Contraindicated (2)

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir, ethinylestradiol. unspecified interaction mechanism. Contraindicated. Potential for increased ALT; contraceptive failure may occur when coadministered with protease inhibitors (ritonavir).

              ethinylestradiol, ombitasvir/paritaprevir/ritonavir & dasabuvir. Either increases toxicity of the other by unspecified interaction mechanism. Contraindicated. ALT elevations >5 x ULN (including some >20 x ULN) observed in clinical trials when ethinyl estradiol was coadministered with ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. Discontinue ethinyl estradiol-containing medications before initiating ombitasvir/paritaprevir/ritonavir, and/or dasabuvir. Restart ethinyl estradiol containing medication ~2 weeks after hepatitis C combination drug regimen completed.

            • tranexamic acid oral

              tranexamic acid oral, ethinylestradiol. 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 (71)

            • abametapir

              abametapir will increase the level or effect of norgestrel 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 ethinylestradiol 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.

            • amobarbital

              amobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • bosentan

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

            • anastrozole

              ethinylestradiol decreases effects of anastrozole by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Anastrozole should not be given concurrently with any estrogens or estrogen-containing products.

            • apalutamide

              apalutamide will decrease the level or effect of ethinylestradiol 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.

            • armodafinil

              armodafinil will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • atazanavir

              atazanavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

            • belzutifan

              belzutifan will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of belzutifan with hormonal contraceptives may lead to contraceptive failure or increased breakthrough bleeding. Advise females of reproductive potential to use effective nonhormonal contraception. Based on animal studies, belzutifan can cause fetal harm.

            • bosentan

              bosentan will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • brigatinib

              brigatinib will decrease the level or effect of ethinylestradiol 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 will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • calaspargase pegol

              calaspargase pegol, ethinylestradiol. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.

            • carbamazepine

              ethinylestradiol will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

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

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

            • conivaptan

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

            • efavirenz

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

            • dexamethasone

              dexamethasone will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • efavirenz

              efavirenz will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • elagolix

              ethinylestradiol 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.

            • elvitegravir

              elvitegravir will decrease the level or effect of ethinylestradiol by unknown mechanism. Avoid or Use Alternate Drug. Consider alternative nonhormonal methods of contraception to add or replace combination oral contraceptive

            • encorafenib

              encorafenib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Since encorafenib can cause fetal harm, advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • enoxaparin

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

            • enzalutamide

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

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use additional or alternative nonhormonal birth control.

            • fexinidazole

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

            • exemestane

              ethinylestradiol decreases effects of exemestane by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Exemestane should not be given concurrently with any estrogens or estrogen-containing products.

            • fedratinib

              ethinylestradiol 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.

            • fexinidazole

              fexinidazole will increase the level or effect of ethinylestradiol by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosamprenavir

              fosamprenavir, ethinylestradiol. unspecified interaction mechanism. Avoid or Use Alternate Drug. Coadministration may decrease amprenavir AUC, and may lead to loss of virologic response. Coadministration of fosamprenavir with ethinyl estradiol may alter hormone levels. Alternative methods of nonhormonal contraception are recommended.

            • fosphenytoin

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

            • griseofulvin

              griseofulvin will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • heparin

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

            • idelalisib

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

            • indinavir

              indinavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

            • isavuconazonium sulfate

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

            • ivosidenib

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

            • lesinurad

              lesinurad decreases effects of ethinylestradiol 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.

            • letrozole

              ethinylestradiol decreases effects of letrozole by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Letrozole should not be given concurrently with any estrogens or estrogen-containing products.

            • lonafarnib

              ethinylestradiol 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, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

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

            • lorlatinib

              lorlatinib will decrease the level or effect of norgestrel 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.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of ethinylestradiol by unspecified interaction mechanism. 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).

            • metyrapone

              ethinylestradiol decreases effects of metyrapone by unspecified interaction mechanism. Avoid or Use Alternate Drug. A subtherapeutic response to metyrapone can be seen in patients on estrogens, including oral contraceptives, that contain estrogen therapy. It may be advisable to discontinue estrogens prior to and during metyrapone administration.

            • mifepristone

              mifepristone decreases effects of norgestrel by pharmacodynamic antagonism. Contraindicated. Backup contraceptive method recommended.

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

            • mobocertinib

              mobocertinib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of mobocertinib with hormonal contraceptives may lead to contraceptive failure or increased breakthrough bleeding. Advise females of reproductive potential to use effective non-hormonal contraception.

            • phenytoin

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

            • modafinil

              modafinil will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • mycophenolate

              mycophenolate decreases effects of ethinylestradiol by unknown mechanism. Avoid or Use Alternate Drug. Patients should consider using an alternative or additional form of contraception.

            • nelfinavir

              nelfinavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

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

            • nevirapine

              nevirapine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • pentobarbital

              pentobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • phenobarbital

              phenobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • phenytoin

              phenytoin will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • primidone

              primidone will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • quinidine

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

            • ranolazine

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

            • rifabutin

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

              rifabutin will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • rifampin

              rifampin will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • rifapentine

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

            • rifapentine

              rifapentine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • ritonavir

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

              ritonavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

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

            • saquinavir

              saquinavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

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

            • tipranavir

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

            • secobarbital

              secobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • St John's Wort

              St John's Wort will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • sugammadex sodium

              sugammadex sodium decreases effects of ethinylestradiol 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.

            • tipranavir

              tipranavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

            • topiramate

              topiramate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • tucatinib

              tucatinib will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              tucatinib will increase the level or effect of ethinylestradiol 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 ethinylestradiol 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

              ethinylestradiol will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. The use of estrogen-containing contraceptives and coumarin derivatives should be avoided to avoid risk of thromboembolic disorders.

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

            Monitor Closely (121)

            • albiglutide

              ethinylestradiol 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.

            • alosetron

              ethinylestradiol will increase the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • alprazolam

              ethinylestradiol will increase the level or effect of alprazolam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.

            • aminocaproic acid

              ethinylestradiol, aminocaproic acid. Other (see comment). Use Caution/Monitor. Comment: Concomitant use may lead to additive hypercoagulability. Estrogens increase clotting factor production and platelet aggregation; aminocaproic acid inhibits fibrinolysis and activity of plasminogen.

            • amobarbital

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

            • amoxicillin

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

            • ampicillin

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

            • artemether/lumefantrine

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

            • atogepant

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

            • atorvastatin

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

            • axitinib

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

            • bendamustine

              ethinylestradiol increases levels of bendamustine by decreasing metabolism. Use Caution/Monitor. Bendamustine is metabolized to minimally active metabolites by CYP1A2. Ethinyl estradiol is a weak CYP1A2 inhibitor and concurrent administration may increase bendamustine concentrations in plasma. .

            • caffeine

              ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cefaclor

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

            • cefazolin

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

            • cefdinir

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

            • cefepime

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

            • cefixime

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

            • cefotaxime

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

            • ceftazidime

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

            • cefuroxime

              cefuroxime will decrease the level or effect of ethinylestradiol 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 ethinylestradiol 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 ethinylestradiol by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Advise women to use additional or alternative non-hormonal birth control when concomitantly using cenobamate with oral contraceptives.

            • cephalexin

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

            • chloramphenicol

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

            • cimetidine

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

            • ciprofloxacin

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

            • clindamycin

              clindamycin will decrease the level or effect of ethinylestradiol 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 ethinylestradiol 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.

            • clonazepam

              ethinylestradiol will increase the level or effect of clonazepam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.

            • cyclosporine

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

            • dabrafenib

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

            • darunavir

              darunavir will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • dasatinib

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

            • deferasirox

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

            • demeclocycline

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

            • diazepam

              ethinylestradiol will increase the level or effect of diazepam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.

            • dicloxacillin

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

            • elagolix

              elagolix will decrease the level or effect of ethinylestradiol 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.

            • eltrombopag

              ethinylestradiol will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

            • erythromycin base

              erythromycin base will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • erythromycin lactobionate

              erythromycin lactobionate will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • erythromycin stearate

              erythromycin stearate will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • etravirine

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

              etravirine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • exenatide injectable solution

              ethinylestradiol, 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. .

            • lamotrigine

              norgestrel 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.

            • exenatide injectable suspension

              ethinylestradiol, 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 ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • finerenone

              ethinylestradiol 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.

            • flibanserin

              ethinylestradiol 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.

            • fluconazole

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

            • fluvoxamine

              ethinylestradiol will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • fostemsavir

              fostemsavir will increase the level or effect of ethinylestradiol by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir. Do not ethinyl estradiol dose of exceed 30 mcg/day.

            • gemifloxacin

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

            • green tea

              ethinylestradiol increases levels of green tea by decreasing elimination. Use Caution/Monitor.

            • hemin

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

            • hyaluronidase

              ethinylestradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

            • iloperidone

              iloperidone increases levels of ethinylestradiol 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.

            • insulin aspart

              ethinylestradiol decreases effects of insulin aspart 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.

            • insulin degludec

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

            • insulin degludec/insulin aspart

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

            • insulin detemir

              ethinylestradiol decreases effects of insulin detemir 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.

            • insulin glargine

              ethinylestradiol decreases effects of insulin glargine 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.

            • insulin glulisine

              ethinylestradiol decreases effects of insulin glulisine 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.

            • insulin inhaled

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

            • insulin lispro

              ethinylestradiol decreases effects of insulin lispro 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.

            • insulin NPH

              ethinylestradiol decreases effects of insulin NPH 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.

            • insulin regular human

              ethinylestradiol decreases effects of insulin regular human 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.

            • isavuconazonium sulfate

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

            • istradefylline

              istradefylline will increase the level or effect of ethinylestradiol 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 ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors such as itraconazole may increase plasma hormone levels.

            • ketoconazole

              ketoconazole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors such as ketoconazole may increase plasma hormone levels.

            • lamotrigine

              ethinylestradiol decreases levels 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

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

            • lemborexant

              ethinylestradiol 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 ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • liraglutide

              ethinylestradiol 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 ethinylestradiol 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

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

            • lorlatinib

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

            • lumefantrine

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

            • metformin

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

            • metronidazole

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

            • mexiletine

              ethinylestradiol will increase the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • midazolam

              ethinylestradiol will increase the level or effect of midazolam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.

            • midazolam intranasal

              ethinylestradiol 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 ethinylestradiol by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.

            • minocycline

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

            • mitotane

              mitotane decreases levels of ethinylestradiol 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.

            • moxifloxacin

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

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

            • neomycin PO

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

            • phenobarbital

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

            • nicardipine

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

            • nilotinib

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

            • nitrofurantoin

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

            • olanzapine

              ethinylestradiol will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • paromomycin

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

            • penicillin G aqueous

              penicillin G aqueous decreases levels of ethinylestradiol by increasing metabolism. Use Caution/Monitor. Risk of oral contraceptive failure.

            • penicillin VK

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

            • pioglitazone

              pioglitazone decreases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.

            • posaconazole

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

            • primidone

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

            • quinupristin/dalfopristin

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

            • ramelteon

              ethinylestradiol will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • rasagiline

              ethinylestradiol will increase the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Recommended dose of rasagiline is 0.5mg daily in combination with CYP1A2 inhibitors.

            • ribociclib

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

            • rifampin

              rifampin will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of nonhormonal contraceptives advised

            • romidepsin

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

            • ropinirole

              ethinylestradiol will increase the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              ethinylestradiol increases levels of ropinirole by unspecified interaction mechanism. Use Caution/Monitor.

            • rucaparib

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

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

            • rufinamide

              rufinamide decreases effects of ethinylestradiol 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. .

            • secobarbital

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

            Minor (23)

            • amitriptyline

              ethinylestradiol, 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

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

            • antipyrine

              ethinylestradiol will increase the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • asenapine

              ethinylestradiol will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • clarithromycin

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

            • clomipramine

              ethinylestradiol will increase the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • desipramine

              ethinylestradiol, desipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • dosulepin

              ethinylestradiol, dosulepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • doxepin

              ethinylestradiol, doxepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • duloxetine

              ethinylestradiol will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • enasidenib

              enasidenib, ethinylestradiol. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.

            • eplerenone

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

            • felbamate

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

            • frovatriptan

              ethinylestradiol will increase the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • imipramine

              ethinylestradiol, imipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • mineral oil

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

            • naratriptan

              ethinylestradiol increases effects of naratriptan by unspecified interaction mechanism. Minor/Significance Unknown. The clinical implication of these interactions is unknown.

            • nefazodone

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

            • nortriptyline

              ethinylestradiol, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • protriptyline

              ethinylestradiol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • ramelteon

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

            • ribociclib

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

            • rosuvastatin

              rosuvastatin increases levels of ethinylestradiol by unspecified interaction mechanism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Edema

            Weakness

            Amenorrhea

            Breakthrough bleeding

            Change in menstrual flow

            Spotting

            Anorexia

            Frequency Not Defined

            DVT

            Thrombophlebitis

            Depression

            Dizziness

            Headache

            Nervousness

            Somnolence

            Breast tenderness

            Galactorrhea

            Abdominal pain

            Nausea

            Vomiting

            Change in weight

            Cholestatic jaundice

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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 with age (>35 yr) and 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

            Receiving hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir

            Cautions

            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)

            Discontinue hormonal therapy prior to starting therapy with combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; may restart approximately 2 weeks following completion of treatment with combination drug regimen

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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 with 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

            Ethinylestradiol (EE): Reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increase synthesis of DNA, RNA, and various proteins in target tissues

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

            Pharmacokinetics

            Half-Life: 28 hr (ethinyl estradiol)

            Protein Bound: Extensively bound to serum albumin (ethinyl estradiol)

            Metabolism: Hepatic CYP3A4 to estriol, estrone (ethinyl estradiol)

            Excretion: Ethinyl estradiol: Urine as conjugates, most estrogens are also excreted in bile and undergo enterohepatic recycling

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            Images

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            Patient Handout

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

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.