Dosing & Uses
Dosage Forms & Strengths
norethindrone acetate/ethinyl estradiol
tablet, hormone replacement
- 0.5mg/2.5mcg (Femhrt, Fyavolv, Jevantique Lo)
- 1mg/5mcg (Jinteli, Fyavolv)
tablet, monophasic
- 1mg/20mcg (Larin 1/20, Loestrin 1/20, Microgestin 1/20, Junel 1/20)
- 1.5mg/30mcg (Hailey 1.5/30, Larin 1.5/30, Loestrin 1.5/30, Microgestin 1.5/30, Junel 1.5/30)
Contraception
Follow Manufacturer's color-coding for sequence
Monophasic formulation
- Take 1 tablet PO qDay for days 1-21, then take 1 inert tablet qDay (or no tablets) for days 22-28, and then restart new pill pack
Biphasic formulation
- Take 1 tablet PO qDay for days 1-10, then take another tablet qDay with a different hormone combination ratio for days 11-21; then take 1 inert tablet qDay for days 22-28
Triphasic formulation
- Take 1 tablet PO qDay for days 1-7; then take another tablet qDay with a different hormone combination ratio for days 8-16; then take 1 tablet of the original formulation ratio qDay for days 17-21; then take 1 inert tablet qDay for days 22-28
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
Hormone Replacement Therapy
Treatment of moderate to severe vasomotor symptoms in menopause with an intact uterus, prevention of osteoporosis in postmenopausal women with an intact uterus
1 tablet (Femhrt 0.5 mg norethindrone/2.5 mcg ethinyl estradiol) PO qDay
Initiate with lowest possible dose and increase only if needed to 1 mg/5 mcg
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
- 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. - tranexamic acid oral
tranexamic acid oral, ethinylestradiol. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of tranexamic acid oral and combination hormonal contraceptives increases thrombotic risk.
Serious - Use Alternative (71)
- acitretin
acitretin decreases effects of norethindrone acetate 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 acetate 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 acetate 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 ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
- brigatinib
brigatinib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration of hormonal contraceptives with brigatinib can result in decreased concentrations and loss of efficacy. Brigatinib can cause fetal harm. Women should use an effective nonhormonal method of contraception during treatment and for at least 4 months after the last brigatinib dose.
- butabarbital
butabarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
- calaspargase pegol
calaspargase pegol, ethinylestradiol. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.
- carbamazepine
ethinylestradiol will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
carbamazepine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
carbamazepine will decrease the level or effect of norethindrone acetate 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). - conivaptan
conivaptan will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of norethindrone acetate 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).
- dexamethasone
dexamethasone will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
- efavirenz
efavirenz will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
- elagolix
ethinylestradiol decreases effects of elagolix by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Based on the mechanism of action of elagolix, estrogen-containing contraceptives are expected to reduce elagolix efficacy. Effects of progestin-only contraceptives on the efficacy of elagolix is unknown. Advise women to use nonhormonal contraceptives during treatment with elagolix and for 1 week after discontinuing elagolix.
- elvitegravir
elvitegravir will decrease the level or effect of ethinylestradiol by unknown mechanism. Avoid or Use Alternate Drug. Consider alternative nonhormonal methods of contraception to add or replace combination oral contraceptive
- encorafenib
encorafenib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Since encorafenib can cause fetal harm, advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.
- enoxaparin
ethinylestradiol decreases effects of enoxaparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- enzalutamide
enzalutamide will decrease the level or effect of 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 acetate 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 acetate 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 acetate 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 acetate 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.
- letrozole
ethinylestradiol decreases effects of letrozole by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Letrozole should not be given concurrently with any estrogens or estrogen-containing products.
- lonafarnib
ethinylestradiol will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
- lopinavir
lopinavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .
lopinavir will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of norethindrone acetate 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 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.
mavacamten will decrease the level or effect of norethindrone acetate 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 acetate 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 acetate 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 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 will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia). - primidone
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 acetate 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 acetate 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.
- 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 acetate 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 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 acetate 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. - topiramate
topiramate will decrease the level or effect of norethindrone acetate 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).
- 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, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .
- topiramate
topiramate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.
- tucatinib
tucatinib will increase the level or effect of 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 acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling. - voxelotor
voxelotor will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
voxelotor will increase the level or effect of norethindrone acetate 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 (161)
- albiglutide
norethindrone acetate 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.
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.
- atazanavir
atazanavir, norethindrone acetate. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.
- 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.
- amoxicillin
amoxicillin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.
- ampicillin
ampicillin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atogepant
ethinylestradiol will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
atorvastatin will increase the level or effect of ethinylestradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- axitinib
ethinylestradiol increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bendamustine
ethinylestradiol increases levels of bendamustine by decreasing metabolism. Use Caution/Monitor. Bendamustine is metabolized to minimally active metabolites by CYP1A2. Ethinyl estradiol is a weak CYP1A2 inhibitor and concurrent administration may increase bendamustine concentrations in plasma. .
- caffeine
ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- cefaclor
cefaclor will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefadroxil
cefadroxil will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefazolin
cefazolin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefdinir
cefdinir will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefepime
cefepime will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefixime
cefixime will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefotaxime
cefotaxime will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefprozil
cefprozil will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- ceftazidime
ceftazidime will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- ceftibuten
ceftibuten will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefuroxime
cefuroxime will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
cenobamate will decrease the level or effect of ethinylestradiol by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Advise women to use additional or alternative non-hormonal birth control when concomitantly using cenobamate with oral contraceptives.
cenobamate will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate. - cephalexin
cephalexin will decrease the level or effect of 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 acetate 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.
- cyclosporine
ethinylestradiol increases levels of cyclosporine by unknown mechanism. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of norethindrone acetate 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 acetate 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 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.
- 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
norethindrone acetate, 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. .
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.
norethindrone acetate, 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 acetate 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.
- iloperidone
iloperidone increases levels of norethindrone acetate 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.
- flibanserin
ethinylestradiol will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
- fluconazole
fluconazole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluvoxamine
ethinylestradiol will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- fostemsavir
fostemsavir will increase the level or effect of ethinylestradiol by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir. Do not ethinyl estradiol dose of exceed 30 mcg/day.
- gemifloxacin
gemifloxacin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- grapefruit
grapefruit will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- green tea
ethinylestradiol increases levels of green tea by decreasing elimination. Use Caution/Monitor.
- hemin
ethinylestradiol decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.
- hyaluronidase
ethinylestradiol decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.
- iloperidone
iloperidone increases levels of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- insulin aspart
ethinylestradiol decreases effects of insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- insulin degludec
ethinylestradiol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.
norethindrone acetate decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Progestins 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 acetate 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 acetate 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 acetate 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.
- lenacapavir
lenacapavir will increase the level or effect of norethindrone acetate 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.
- 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.
- 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.
norethindrone acetate 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.
- maraviroc
norethindrone acetate increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.
- 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 - lorlatinib
lorlatinib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lumefantrine
lumefantrine will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metformin
ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- metronidazole
metronidazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- mexiletine
ethinylestradiol will increase the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- midazolam
ethinylestradiol will increase the level or effect of midazolam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.
- midazolam intranasal
ethinylestradiol will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
- mifepristone
mifepristone decreases effects of norethindrone acetate by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.
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.
- rucaparib
rucaparib will increase the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- 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.
- 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.
- 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.
- rufinamide
rufinamide decreases effects of norethindrone acetate 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 acetate. 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 acetate. 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 acetate 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 acetate 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.
- 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.
Minor (31)
- acetazolamide
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.
- 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.
- desipramine
ethinylestradiol, desipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.
- dosulepin
ethinylestradiol, dosulepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.
- doxepin
ethinylestradiol, doxepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.
- duloxetine
ethinylestradiol will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- enasidenib
enasidenib, ethinylestradiol. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.
- eplerenone
ethinylestradiol will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- felbamate
felbamate decreases levels of ethinylestradiol by unknown mechanism. Minor/Significance Unknown.
- frovatriptan
ethinylestradiol will increase the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- imipramine
ethinylestradiol, imipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.
- larotrectinib
larotrectinib will increase the level or effect of ethinylestradiol 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.
- rosuvastatin
rosuvastatin increases levels of ethinylestradiol by unspecified interaction mechanism. Minor/Significance Unknown.
- ruxolitinib
ethinylestradiol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
ethinylestradiol will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- tizanidine
ethinylestradiol increases levels of tizanidine by unspecified interaction mechanism. Minor/Significance Unknown.
- trazodone
ethinylestradiol, trazodone. 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.
- trimipramine
ethinylestradiol, trimipramine. 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.
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
Estrogen plus progestin therapy
-
Cardiovascular disorders and dementia risks
- The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risk of pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA)
- The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women >65 during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo; unknown whether this finding applies to younger postmenopausal women
- Do not use estrogen plus progestogen therapy for prevention of cardiovascular disease or dementia
-
Breast cancer
- The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer
- Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI; therefore, relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known
- Without such data, it is not possible to definitively exclude these risks or determine extent of these risks for other products
- Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account individual risk profile; prescribe estrogens with or without progestogens at lowest effective doses and for shortest duration consistent with treatment goals and risks for individual woman
Estrogen alone therapy
-
Endometrial cancer
- There is increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens; adding a progestogen to estrogen therapy has been shown to reduce risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
- Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding
-
Cardiovascular disorders and dementia risks
- The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo
- The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo
- It is unknown whether finding applies to younger postmenopausal women
- Do not use estrogen-alone therapy for prevention of cardiovascular disease or dementia
- Only daily oral 0.625 mg CE was studied in estrogen-alone substudy of the WHI; therefore,the relevance of WHI findings regarding adverse cardiovascular events and dementia to lowerCE doses, other routes of administration, or other estrogen-alone products is not known
- Without such data, it is not possible to definitively exclude risks or determine extent of these risks for other products; discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile
- Prescribe estrogens with or without progestogens at lowest effective doses and for shortest duration consistent with treatment goals and risks for individual woman
Contraindications
Documented hypersensitivity
Active or history of breast cancer
Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
Estrogen-dependent neoplasia
Liver disease, liver tumors
Undiagnosed abnormal vaginal bleeding
Uncontrolled hypertension
Diabetes mellitus with vascular involvement
Jaundice with prior oral contraceptive use
Cautions
Acitretin inhibits contraceptive efficacy of norethindrone preparations
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
Carefully observe women with history of depression and discontinue therapy if depression recurs to a serious degree
Discontinue 4 week before major surgery or prolonged immobilization
Patients on warfarin, oral anticoagulants (increase in anticoagulant dose may be warranted)
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
Some studies suggest that oral contraceptive use has been associated with an increase in risk of cervical intraepithelial neoplasia in some populations of women
Benign hepatic adenomas are associated with oral contraceptive use, although incidence is rare in the United States
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema
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)
Breast cancer
- Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between ever (current or past) use of COCs and risk of breast cancer
- Some studies report a small increase in risk of breast cancer among current or recent users(<6 months since last use) and current users with longer duration of COC use
- A 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
Carbohydrates and lipid metabolic effects
- Oral contraceptives shown to cause glucose intolerance in a significant percentage of users; oral contraceptives containing >75 mcg of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance
- Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents; however, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose
- Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives
Elevated blood pressure
- Data from the Royal College of General Practitioners (18) and subsequent randomized trials have shown that incidence of hypertension increases with increasing concentrations of progestogens
- Women with a history of hypertension or hypertension-related diseases or renal disease should be encouraged to use another method of contraception; if women elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued
- For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in occurrence of hypertension among ever and never users
Cigarette smoking and 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
Pregnancy & Lactation
Pregnancy
Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy; studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy
Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy; oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion
It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use; if the patient has not adhered to prescribed schedule, possibility of pregnancy should be considered at time of first missed period; oral contraceptive use should be discontinued if pregnancy is confirmed
Lactation
Small amounts of oral contraceptive steroids identified in the milk of nursing mothers, and a few adverse effects on child reported, including jaundice and breast enlargement; in addition, oral contraceptives given in postpartum period may interfere with lactation by decreasing quantity and quality of breast milk
If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child
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 acetate: progestin; inhibits gonadotropin secretion of gonadotropins from pituitary; prevents follicular maturation & ovulation, stimulates growth of mammary tissues
Absorption
Peak Plasma Time: 8 hr (EE); 1-2 hr (norethindrone)
Distribution
Ethinyl Estradiol: Vd: 2-4 L/Kg
Protein binding: Ethinyl estradiol 80%; norethindrone 61%
Metabolism
Both components are metabolized in the liver; estradiol undergoes extensive first-pass metabolism
Ethinyl estradiol metabolites: Estriol, estrone
Norethindrone metabolites: Sulfate and glucuronide metabolites (inactive)
Elimination
Half-Life: Ethinyl Estradiol: PO:19-24 hr
Excretion
- Ethinyl estradiol: Urine as conjugates, most estrogens are also excreted in bile and undergo enterohepatic recycling
- Norethindrone: Urine: 33-81%; feces 35-43%
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Formulary
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