Dosing & Uses
Dosage Forms & Strengths
norethindrone/ethinyl estradiol
tablet, monophasic
- 0.4 mg/35mcg (Balziva-28, Briellyn, Gildagia, Ovcon 35 [DSC], Philith, Rhuzdah, Vyfemla, Zenchent)
- 0.5mg/35mcg (Cyclafem 0.5/35, Cyonanz, Modicon, Necon 0.5/35, Nortrel 0.5/35, Wera)
- 1mg/35mcg (Alyacen 1/35, Brevicon, Cyclafem 1/35, Dasetta 1/35, Necon 1/35, Norinyl 1+35, Nortrel 1/35, Nylia 1/35, Ortho Novum 1/35, Pirmella 1/35)
- 1mg/50mcg (Brevicon)
tablet, biphasic (Necon 10/11)
- 0.5mg/35mcg (10 tabs)
- 1mg/35mcg (11 tabs)
- Inert tabs (7 tabs)
tablet, multiphasic (Aranelle, Leena, Tri-Norinyl)
- 0.5mg/35mcg (7 tabs)
- 1mg/35mcg (9 tabs)
- 0.5mg/35mcg (5 tabs)
- Inert tabs (7 tabs)
tablet, triphasic (Alyacen 7/7/7, Cyclafem 7/7/7, Dasetta 7/7/7, Nortrel 7/7/7, Nylia 7/7/7, Ortho Novum 7/7/7, Pirmella 7/7/7)
- 0.5mg/35mcg (7 tabs)
- 0.75mg/35mcg (7 tabs)
- 1mg/35mcg (7 tabs)
- Inert tabs (7 tabs)
Oral Contraceptive
Monophasic kit: 1 active tablet PO qDay for days 1-21, then 1 inert tablet qDay (or no tablets) for Days 22-28, and then restart with new pill pack
See package insert for multiphasic, biphasic, and triphasic dosing
Follow Manufacturer's color-coding for sequence
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
Not recommended premenarche
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (3)
- fezolinetant
ethinylestradiol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
- mifepristone
mifepristone will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC), ethinylestradiol. unspecified interaction mechanism. Contraindicated. Potential for increased ALT; contraceptive failure may occur when coadministered with protease inhibitors (ritonavir).
ethinylestradiol, ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC). 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.
Serious - Use Alternative (74)
- acitretin
acitretin decreases effects of norethindrone by unknown mechanism. Contraindicated. Contraceptive failure may result.
- 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.
- 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.
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. - 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.
- belzutifan
belzutifan will decrease the level or effect of norethindrone 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.
- 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
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 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.
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.
- 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).
- 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 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.
- 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.
efavirenz will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - 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.
- 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).
- 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 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.
- 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
fexinidazole will increase the level or effect of 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 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).
- 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
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 - 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. .
- ivosidenib
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.
- 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.
- leniolisib
leniolisib will increase the level or effect of ethinylestradiol by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
- 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.
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. - 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.
- 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.
- 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. - 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).
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). - mavacamten
mavacamten will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.
mavacamten will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose. - 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.
- 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).
- mifepristone
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.
- 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.
- omaveloxolone
omaveloxolone will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Omaveloxolone may reduce efficacy of hormonal contraceptives (eg, pill, patch, ring), implants, and progestin-only pills owing to weak CYP3A4 induction.
- 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 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 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 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 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.
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). - quinidine
quinidine will increase the level or effect of ethinylestradiol by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- 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).
- ranolazine
ethinylestradiol will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- repotrectinib
repotrectinib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- rifabutin
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 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 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 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 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 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). - ritonavir
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 ethinylestradiol 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.
- 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. - 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 will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
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 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).
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 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.
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 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.
Monitor Closely (171)
- 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 norethindrone 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.
- 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.
- 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 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 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.
- 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.
- ceritinib
ceritinib will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- 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.
- 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
ethinylestradiol increases levels of cyclosporine by unknown mechanism. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
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.
- 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.
- 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.
- 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 will increase the level or effect of ethinylestradiol by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. - 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.
- etravirine
etravirine will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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 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. .
- 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 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 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.
- fosamprenavir
fosamprenavir, norethindrone. unspecified interaction mechanism. Use Caution/Monitor. Variable effect on norethindrone. Use non-hormonal contraception.
- 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.
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.
- 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
norethindrone decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.
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.
norethindrone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins 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 inhaled
norethindrone decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.
- 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 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.
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.
- lamotrigine
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.
- 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.
- lenacapavir
lenacapavir will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
lenacapavir will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates. - letermovir
letermovir increases levels of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- levoketoconazole
levoketoconazole 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.
- 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 (DSC)
lixisenatide (DSC) 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.
- lonapegsomatropin
ethinylestradiol will decrease the level or effect of lonapegsomatropin by Other (see comment). Use Caution/Monitor. Oral estrogens may reduce serum insulin-like growth factor-1 response to lonapegsomatropin. Patients receiving oral estrogen replacement may require higher lonapegsomatropin dosages.
ethinylestradiol will decrease the level or effect of lonapegsomatropin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be required - lopinavir
lopinavir will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- maraviroc
norethindrone increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.
- metformin
ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
norethindrone 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.
- mifepristone
mifepristone decreases effects of norethindrone by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.
- 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.
- momelotinib
momelotinib increases toxicity of ethinylestradiol by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of nonhormonal contraceptives advised while in therapy - nelfinavir
nelfinavir will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- 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.
- nirmatrelvir
nirmatrelvir will decrease the level or effect of ethinylestradiol by increasing metabolism. Modify Therapy/Monitor Closely. Consider using additional nonhormonal contraceptive method for remainder of cycle. Mechanism unknown, but possibly by ritonavir CYP2C9 or CYP1A2 induction.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will decrease the level or effect of ethinylestradiol by increasing metabolism. Modify Therapy/Monitor Closely. Consider using additional nonhormonal contraceptive method for remainder of cycle. Mechanism unknown, but possibly by ritonavir CYP2C9 or CYP1A2 induction.
- 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.
- oteseconazole
oteseconazole will increase the level or effect of ethinylestradiol by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- 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.
- 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.
- ritonavir
ritonavir will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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 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 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. . - selegiline
ethinylestradiol increases levels of selegiline by Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives inhibit the N demethylatin of selegiline.
- 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
ethinylestradiol increases levels of selegiline transdermal by Other (see comment). Use Caution/Monitor. Comment: Oral contraceptives inhibit the N demethylatin of selegiline.
- siltuximab
siltuximab, ethinylestradiol. 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.
- somapacitan
ethinylestradiol will decrease the level or effect of somapacitan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be required
- somatrogon
ethinylestradiol will decrease the level or effect of somatrogon by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be required
- somatropin
ethinylestradiol will decrease the level or effect of somatropin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be required
- 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, ethinylestradiol. 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. - sulfadiazine
sulfadiazine 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.
- tazemetostat
tazemetostat will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- sulfamethoxazole
sulfamethoxazole 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.
- sulfisoxazole
sulfisoxazole 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.
- tacrolimus
ethinylestradiol will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ethinylestradiol 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 ethinylestradiol 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 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. - teriflunomide
teriflunomide increases levels of ethinylestradiol by unknown mechanism. 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
- tetracycline
tetracycline 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.
- theophylline
ethinylestradiol will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- ticarcillin
ticarcillin 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.
- tigecycline
tigecycline 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.
- tinidazole
ethinylestradiol will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tizanidine
ethinylestradiol will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Monitor for tizanidine adverse effects (eg, hypotension or bradycardia)
- tolterodine
ethinylestradiol will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- triazolam
ethinylestradiol will increase the level or effect of triazolam 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.
- trimethoprim
trimethoprim 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.
- ursodiol
ethinylestradiol decreases effects of ursodiol by pharmacodynamic antagonism. Use Caution/Monitor.
- valoctocogene roxaparvovec
ethinylestradiol and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- valproic acid
ethinylestradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency
- voriconazole
voriconazole will increase the level or effect of ethinylestradiol 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.
Minor (30)
- acetazolamide
acetazolamide will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
acetazolamide will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - 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.
- anastrozole
anastrozole will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- anastrozole
anastrozole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- cyclophosphamide
cyclophosphamide will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
cyclophosphamide will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 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.
- larotrectinib
larotrectinib will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- larotrectinib
larotrectinib will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- levoketoconazole
levoketoconazole will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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 norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- rosuvastatin
rosuvastatin increases levels of ethinylestradiol by unspecified interaction mechanism. Minor/Significance Unknown.
Adverse Effects
>10%
Edema
Weakness
Anorexia
Amenorrhea
Breakthrough bleeding
Change in menstrual flow
Spotting
Frequency Not Defined
Deep vein thrombosis
Thrombophlebitis
Depression
Dizziness
Headache
Nervousness
Somnolence
Breast tenderness
Galactorrhea
Abdominal pain
Nausea
Vomiting
Weight change
Cholestatic jaundice
Warnings
Black Box Warnings
Cardiovascular Risks
- Estrogens with or without progestins should not be used to prevent cardiovascular disease
- Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 yr) during 5.6 yr of treatment with daily PO conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) compared with placebo
- Estrogens alone: The estrogen alone substudy of the WHI Study reported increased risks of stroke and DVT in postmenopausal women (aged 50-79 yr) during 6.8 yr of treatment with oral conjugated estrogens (0.625 mg/day) alone compared with placebo
Dementia Risks
- Estrogens with or without progestins should not be used to prevent dementia
- Women's Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 4 yr of treatment w/ daily CE 0.625 mg combined with MPA 2.5 mg, compared with placebo
- Estrogens alone: A substudy of the WHIMS reported an increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 5.2 yr of treatment with conjugated estrogens 0.625 mg alone compared with placebo
- Unknown whether these findings apply to younger postmenopausal women
Dose & Duration
- In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations adn dosage forms of estrogens and progestins
- Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks
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 uterine bleeding
Uncontrolled hypertension (ie, persistent BP values >160 mm Hg systolic or >100 mg Hg diastolic)
Diabetes mellitus with vascular involvement
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
Cautions
Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception
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, significant blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery
Monitor prediabetic and diabetic women taking eithinyl estradiol/norethindrone; consider alternative contraceptive method for women with uncontrolled dyslipidemia
Risk of thromboembolic disease associated with oral contraceptives gradually disappears after combined oral contraceptive (COC) use is stopped; VTE risk is highest in first year of use and when restarting hormonal contraception after a break of four weeks or longer
Discontinue 4 week before major surgery or prolonged immobilization
If thrombotic event occurs, stop at least 4 wk before through 2 wk after major surgery; start no earlier than 4 weeks after delivery, in women who are not breastfeeding
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
Evaluate significant change in headaches and discontinue therapy if indicated
Evaluate irregular bleeding or amenorrhea
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
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)
Pregnancy & Lactation
Pregnancy
There is no use for contraception in pregnancy; therefore, this drug should be discontinued during pregnancy; epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy
Lactation
Contraceptive hormones and/or metabolites are present in human milk; COCs can reduce milk production in breast-feeding females; this reduction can occur at any time but is less likely to occur once breast-feeding is well-established
When possible, advise the nursing female to use other methods of contraception until she discontinues breast-feeding; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or from underlying maternal condition
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.Pharmacology
Mechanism of Action
Ethinyl Estradiol (EE): Reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increases synthesis of DNA, RNA, and various proteins in target tissues
Norethindrone: progestin; inhibits gonadotropin secretion of gonadotropins from pituitary; prevents follicular maturation and ovulation, stimulates growth of mammary tissues
Pharmacokinetics
Peak Plasma Time: 8 hr (ethinyl estradiol ); 1-2 hr (norethindrone)
Protein binding: 80% (ethinyl estradiol); 61% (norethindrone)
Both components are metabolized in the liver; estradiol undergoes extensive first-pass metabolism
Bioavailability: 43-55% (ethinyl estradiol)
Vd: 2-4 L/kg (ethinyl estradiol)
Ethinyl estradiol metabolites: Estriol, estrone
Norethindrone metabolites: Sulfate and glucuronide metabolites (inactive)
Half-life: 4-13 hr (norethindrone); 19-24 hr (ethinyl estradiol)
Excretion
- Ethinyl estradiol: Urine as conjugates, most estrogens are also excreted in bile and undergo enterohepatic recycling
- Norethindrone: 33-81% (urine); 35-43% (feces)
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Formulary
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