Dosing & Uses
Dosage Forms & Strengths
vaginal cream
- 0.625mg/g
Atrophic Vaginitis and Kraurosis Vulvae
Administer cyclic regimen (daily for 21 days followed by 7 days off) intravaginally
Start at 0.5 g dosage strength; may adjust dosage (0.5 to 2 g) based on individual response
Moderate to Severe Dyspareunia
Treats symptom of vulvar and vaginal atrophy due to menopause
0.5 g intravaginally in a twice-weekly (eg, Monday and Thursday) continuously or in a cyclic regimen of daily administration for 21 days followed by 7 days off
Dosing Considerations
In postmenopausal women with a uterus, a progestin should also be considered to reduce risk of endometrial cancer
Women without a uterus do not need a progestin; in some cases, however, hysterectomized women with a history of endometriosis may need a progestin
Use of estrogen-alone, or in combination with a progestin, should be with lowest effective dose and for shortest duration consistent with treatment goals and risks for the individual
Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary
Administration
Plastic applicator calibrated in 0.5 g increments to a maximum of 2 g
Not indicated
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (15)
- carbamazepine
carbamazepine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cimetidine
cimetidine will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin base
erythromycin base will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- itraconazole
itraconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ketoconazole
ketoconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- levoketoconazole
levoketoconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinidine
quinidine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (114)
- albiglutide
conjugated estrogens, vaginal decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- ambrisentan
ambrisentan will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ambrisentan will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - amiodarone
amiodarone will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amobarbital
amobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- anastrozole
conjugated estrogens, vaginal decreases effects of anastrozole by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.
- antithrombin alfa
conjugated estrogens, vaginal decreases effects of antithrombin alfa by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- antithrombin III
conjugated estrogens, vaginal decreases effects of antithrombin III by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- aprepitant
aprepitant will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- argatroban
conjugated estrogens, vaginal decreases effects of argatroban by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- armodafinil
armodafinil will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atazanavir
atazanavir, conjugated estrogens, vaginal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated . Use alternatives if available.
- atorvastatin
atorvastatin will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- axitinib
conjugated estrogens, vaginal decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bemiparin
conjugated estrogens, vaginal decreases effects of bemiparin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- bivalirudin
conjugated estrogens, vaginal decreases effects of bivalirudin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- bosentan
bosentan will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- budesonide
budesonide will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butabarbital
butabarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cannabidiol
cannabidiol, conjugated estrogens, vaginal. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.
- chloramphenicol
chloramphenicol increases levels of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May increase side effects.
- clarithromycin
clarithromycin will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- clotrimazole
clotrimazole will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- conivaptan
conivaptan will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cortisone
cortisone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 and transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclosporine
cyclosporine will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
cyclosporine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - dalteparin
conjugated estrogens, vaginal decreases effects of dalteparin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- darifenacin
darifenacin will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- darunavir
darunavir will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dasatinib
dasatinib will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- deferasirox
deferasirox will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dexamethasone
dexamethasone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- DHEA, herbal
DHEA, herbal will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diltiazem
diltiazem will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
dronedarone will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - efavirenz
efavirenz will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- enoxaparin
conjugated estrogens, vaginal decreases effects of enoxaparin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- erythromycin base
erythromycin base will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- exenatide injectable solution
conjugated estrogens, vaginal decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- exenatide injectable suspension
conjugated estrogens, vaginal decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- felodipine
felodipine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fluconazole
fluconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fludrocortisone
fludrocortisone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fondaparinux
conjugated estrogens, vaginal decreases effects of fondaparinux by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- fosamprenavir
fosamprenavir will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosaprepitant
fosaprepitant will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
fosphenytoin will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - grapefruit
grapefruit will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- griseofulvin
griseofulvin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- hemin
conjugated estrogens, vaginal decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.
- heparin
conjugated estrogens, vaginal decreases effects of heparin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- hyaluronidase
conjugated estrogens, vaginal decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Enhanced tissue resistance to hyaluronidase.
- hydrocortisone
hydrocortisone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- indinavir
indinavir will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
indinavir will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - ketoconazole
ketoconazole will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lamotrigine
conjugated estrogens, vaginal decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.
- lapatinib
lapatinib will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
lapatinib will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - levoketoconazole
levoketoconazole will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- liraglutide
conjugated estrogens, vaginal decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- loratadine
loratadine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lovastatin
lovastatin will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lumefantrine
lumefantrine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- maraviroc
conjugated estrogens, vaginal increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .
- marijuana
marijuana will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- meropenem/vaborbactam
meropenem/vaborbactam will decrease the level or effect of conjugated estrogens, vaginal by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- methylprednisolone
methylprednisolone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metronidazole
metronidazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- miconazole vaginal
miconazole vaginal will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nafcillin
nafcillin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nefazodone
nefazodone will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nelfinavir
nelfinavir will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nevirapine
nevirapine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nifedipine
nifedipine will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
nifedipine will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nilotinib
nilotinib will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
nilotinib will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nilutamide
nilutamide will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ospemifene
ospemifene, conjugated estrogens, vaginal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pentobarbital
pentobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenindione
conjugated estrogens, vaginal decreases effects of phenindione by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- phenobarbital
phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - phenytoin
phenytoin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. - posaconazole
posaconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- prednisone
prednisone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- primidone
primidone will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- protamine
conjugated estrogens, vaginal decreases effects of protamine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- quercetin
quercetin will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ranolazine
ranolazine will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ritonavir will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - rufinamide
rufinamide will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- secobarbital
secobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- simvastatin
simvastatin will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sirolimus
sirolimus will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- somapacitan
conjugated estrogens, vaginal decreases effects of somapacitan by Other (see comment). Modify Therapy/Monitor Closely. Comment: Oral estrogens may reduce the serum IGF-1 response to somapacitan. Patients may require higher somapacitan dosages. See drug monograph for starting dose recommendations.
- St John's Wort
St John's Wort will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tacrolimus
tacrolimus will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- teniposide
teniposide will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tesamorelin
tesamorelin will decrease the level or effect of conjugated estrogens, vaginal by altering metabolism. Use Caution/Monitor. May decrease efficacy; monitor
- tolvaptan
tolvaptan will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- topiramate
topiramate will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- trazodone
trazodone will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- verapamil
verapamil will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
verapamil will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - voriconazole
voriconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- zafirlukast
zafirlukast will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (35)
- amitriptyline
conjugated estrogens, vaginal, 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
conjugated estrogens, vaginal, amoxapine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- androstenedione
androstenedione increases effects of conjugated estrogens, vaginal by pharmacodynamic synergism. Minor/Significance Unknown.
- ascorbic acid
conjugated estrogens, vaginal decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.
- boron
boron increases levels of conjugated estrogens, vaginal by altering metabolism. Minor/Significance Unknown.
- clomipramine
conjugated estrogens, vaginal, clomipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- cyanocobalamin
conjugated estrogens, vaginal decreases levels of cyanocobalamin by altering metabolism. Minor/Significance Unknown.
- desipramine
conjugated estrogens, vaginal, desipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- dosulepin
conjugated estrogens, vaginal, dosulepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- doxepin
conjugated estrogens, vaginal, doxepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- exemestane
conjugated estrogens, vaginal decreases levels of exemestane by increasing metabolism. Minor/Significance Unknown.
- folic acid
conjugated estrogens, vaginal decreases levels of folic acid by altering metabolism. Minor/Significance Unknown.
- imipramine
conjugated estrogens, vaginal, imipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- isoniazid
isoniazid will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- L-methylfolate
conjugated estrogens, vaginal decreases levels of L-methylfolate by altering metabolism. Minor/Significance Unknown.
- lofepramine
conjugated estrogens, vaginal, lofepramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- magnesium chloride
conjugated estrogens, vaginal decreases levels of magnesium chloride by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.
- magnesium citrate
conjugated estrogens, vaginal decreases levels of magnesium citrate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.
- magnesium hydroxide
conjugated estrogens, vaginal decreases levels of magnesium hydroxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.
- magnesium oxide
conjugated estrogens, vaginal decreases levels of magnesium oxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.
- magnesium sulfate
conjugated estrogens, vaginal decreases levels of magnesium sulfate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage.
- maprotiline
conjugated estrogens, vaginal, maprotiline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- metyrapone
conjugated estrogens, vaginal decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.
- mycophenolate
mycophenolate decreases effects of conjugated estrogens, vaginal by unknown mechanism. Minor/Significance Unknown. Clinical significance unclear.
- nortriptyline
conjugated estrogens, vaginal, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- phytoestrogens
phytoestrogens decreases effects of conjugated estrogens, vaginal by pharmacodynamic antagonism. Minor/Significance Unknown.
- pleurisy root
pleurisy root decreases effects of conjugated estrogens, vaginal by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.
- progesterone, natural
progesterone, natural, conjugated estrogens, vaginal. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Combination may produce breast tenderness.
- protriptyline
conjugated estrogens, vaginal, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- pyridoxine
conjugated estrogens, vaginal decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.
- pyridoxine (Antidote)
conjugated estrogens, vaginal decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.
- ropinirole
conjugated estrogens, vaginal increases levels of ropinirole by unspecified interaction mechanism. Minor/Significance Unknown.
- rose hips
conjugated estrogens, vaginal decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.
- trazodone
conjugated estrogens, vaginal, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- trimipramine
conjugated estrogens, vaginal, trimipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
Adverse Effects
1-10%
Breast pain (4.9%)
Headache (3.5%)
Pelvic pain (2.8%)
Vulvovaginal disorder (2.8%)
Vasodilation (2.1%)
Leukorrhea (2.1%)
Moniliasis (1.4%)
Pain (1.4%)
Muscle cramps (1.4%)
Pruritus (1.4%)
Dysuria (1.4%)
Vaginal hemorrhage (1.4%)
Vaginitis (1.4%)
<1%
Abdominal pain
Dizziness
Breast enlargement
Urinary urgency
Postmarketing Reports
Genitourinary system: Abnormal uterine bleeding or spotting, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis (including vaginal candidiasis), change in cervical secretion, cystitis-like syndrome, application site reactions of vulvovaginal discomfort, (including burning, irritation, and genital pruritus), endometrial hyperplasia, endometrial cancer, precocious puberty, leukorrhea
Breasts: Tenderness, enlargement, pain, discharge, fibrocystic breast changes, breast cancer, gynecomastia in males
Cardiovascular: DVT, PE, MI, stroke, increased BP
Gastrointestinal: Nausea, vomiting, abdominal cramps, bloating, increased incidence of gallbladder disease
Skin: Chloasma that may persist when drug is discontinued, loss of scalp hair, hirsutism, rash
Eyes: Retinal vascular thrombosis, intolerance to contact lenses
Central nervous system: Headache, migraine, dizziness, mental depression, nervousness, mood disturbances, irritability, dementia
Miscellaneous: Increase or decrease in weight, glucose intolerance, edema, arthralgias, leg cramps, changes in libido, urticaria, exacerbation of asthma, increased triglycerides, hypersensitivity
Warnings
Black Box Warnings
Endometrial cancer
- Estrogens increase risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens
- Close clinical surveillance of all women taking estrogens is important
- Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding
- There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than the use of synthetic estrogens at equivalent estrogen doses
Breast cancer
- Using conjugated estrogens in combination with medroxyprogesterone increases risk of invasive breast cancer
Cardiovascular risks
- Estrogens with 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 (MI), stroke, invasive breast cancer, pulmonary embolism (PE), and deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 years) during 5.6 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
- Estrogens alone: A substudy of the WHI study reported increased risk for stroke and DVT in postmenopausal women (aged 50-79 years) during 6.8 years of treatment with daily PO conjugated estrogens (0.625 mg) alone in comparison 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 years during 4 years of treatment with daily PO conjugated estrogens (0.625) mg combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
- Estrogens alone: A substudy of the WHIMS reported increased risk of developing probable dementia in postmenopausal women aged ≥65 years during 5.2 years of treatment with daily PO conjugated estrogens (0.625 mg) alone in comparison with placebo
- Unknown whether these findings apply to younger postmenopausal women
Dose and duration
- In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate, as well as for other combinations and dosage forms of estrogens and progestins
- Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective dosage and for the shortest duration consistent with treatment goals and individual risks
Contraindications
Undiagnosed abnormal genital bleeding
Known, suspected, or history of breast cancer
Known or suspected estrogen-dependent neoplasia
Active DVT, PE, or a history of these conditions
Active arterial thromboembolic disease (eg, stroke, MI), or a history of these conditions
Known anaphylactic reaction or angioedema to conjugated estrogen preparations
Known liver dysfunction or disease
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Known or suspected pregnancy
Cautions
Systemic absorption occurs with use of vaginal cream
Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, may lower incidence of endometrial hyperplasia compared to estrogen treatment alone; endometrial hyperplasia may be a precursor to endometrial cancer
There are possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including increased risk of breast cancer
If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization
Most studies show no significant increased risk of endometrial cancer associated with use of estrogens for <1 year; the greatest risk appears to be associated with prolonged use, with increased risks of 15-to 24-fold for 5 to 10 years or more; this risk has been shown to persist for at least 8-15 years after estrogen therapy discontinued
All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations; in addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results
Risk of cardiovascular, endometrial cancer, breast cancer, and dementia; see Black Box Warnings
Estrogens increase the risk of gallbladder disease
Discontinue estrogen if severe hypercalcemia, severe hypertriglyceridemia occurs
Monitor thyroid function in women on thyroid replacement therapy
Estrogens may be poorly metabolized in women with impaired liver function; for women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued
Hormonal therapy for menopausal symptoms associated with increased risk for ovarian cancer; the exact duration of hormone therapy use associated with increased risk of ovarian cancer, is unknown
Retinal vascular thrombosis has been reported in patients receiving estrogens; discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued
May cause fluid retention; women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogen-alone prescribed
A few cases of malignant transformation of residual endometrial implants reported in women treated post-hysterectomy with estrogen-alone therapy; for women known to have residual endometriosis post-hysterectomy, addition of progestin should be considered
Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur
Rare cases of anaphylaxis and angioedema reported; may exacerbate symptoms of hereditary angioedema
May cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas
Premarin cream may weaken latex condoms; the potential for the vaginal cream to weaken and contribute to the failure of condoms, diaphragms, or cervical caps made of latex or rubber should be considered
Hypothyroidism
- Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women with normal thyroid function can compensate for increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range
- Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy; these women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range
Venous Thromboembolism
- Manage appropriately risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus)
- Should VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately
Pregnancy & Lactation
Pregnancy Category: X
Lactation: Distributed in human breast milk; caution when breast feeding, estrogens may decrease the quantity and quality of milk
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
Estrogens act through binding to nuclear receptors in estrogen-responsive tissues
Absorption
Peak plasma concentration: 42 pg/mL (estrone); 12.8 pg/mL (estradiol)
Peak plasma time: 7.4 hr (estrone); 8.5 hr (estradiol)
AUC: 826 pg•hr/mL (estrone); 231 pg•hr/mL (estradiol)
Distribution
Protein binding: Largely bound to sex hormone binding globulin (SHBG) and albumin
Widely distributed throughout body, higher concentration in sex hormone target organs
Metabolism
Liver
Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is a major urinary metabolite
Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption
Elimination
Excretion: Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates
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Formulary
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