Dosing & Uses
Dosage Forms & Strengths
drospirenone/estradiol
tablet
- 0.25mg/0.5mg
- 0.5mg/1mg
Hormone Replacement Therapy
1 tablet PO daily
Use the lowest dose that will control symptoms
Renal Impairment
Do not administer
Hepatic Impairment
Do not administer
Other Indications & Uses
Hormone replacement therapy for women with intact uterus: Treatment of menopause-associated hot flashes and vulvar/vaginal atrophy
Safety and efficacy not established
Hormone replacement therapy
1 tablet PO daily
Use the lowest dose that will control symptoms
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (2)
- fezolinetant
estradiol 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
- ospemifene
ospemifene, estradiol. Either increases effects of the other by pharmacodynamic synergism. Contraindicated.
Serious - Use Alternative (50)
- amiloride
amiloride and drospirenone both increase serum potassium. Avoid or Use Alternate Drug.
amiloride, drospirenone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia. - anastrozole
estradiol decreases effects of anastrozole by pharmacodynamic antagonism. Contraindicated. Estrogen may diminish the pharmacologic action of anastrozole. Coadministration not recommended.
- antithrombin alfa
estradiol decreases effects of antithrombin alfa by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- antithrombin III
estradiol decreases effects of antithrombin III by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- apalutamide
apalutamide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- argatroban
estradiol decreases effects of argatroban by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- belzutifan
belzutifan will decrease the level or effect of drospirenone 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.
- bemiparin
estradiol decreases effects of bemiparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- bivalirudin
estradiol decreases effects of bivalirudin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- calaspargase pegol
calaspargase pegol, drospirenone. 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
carbamazepine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cimetidine
cimetidine will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dalteparin
estradiol decreases effects of dalteparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- enoxaparin
estradiol decreases effects of enoxaparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- enzalutamide
enzalutamide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eplerenone
drospirenone, eplerenone. Mechanism: pharmacodynamic synergism. Contraindicated. Hyperkalemia.
- erdafitinib
erdafitinib will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- erythromycin base
erythromycin base will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
drospirenone 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 estradiol 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.
- fondaparinux
estradiol decreases effects of fondaparinux by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- givosiran
givosiran will increase the level or effect of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- heparin
estradiol decreases effects of heparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- idelalisib
idelalisib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- isavuconazonium sulfate
isavuconazonium sulfate will increase the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of estradiol 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.
- lonafarnib
drospirenone 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.
- mavacamten
mavacamten will decrease the level or effect of drospirenone 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.
- mobocertinib
mobocertinib will decrease the level or effect of drospirenone 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.
- nefazodone
nefazodone will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- omaveloxolone
omaveloxolone will decrease the level or effect of drospirenone 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.
- pacritinib
estradiol will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenindione
estradiol decreases effects of phenindione by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- potassium acid phosphate
drospirenone and potassium acid phosphate both increase serum potassium. Avoid or Use Alternate Drug.
- potassium chloride
drospirenone and potassium chloride both increase serum potassium. Avoid or Use Alternate Drug.
- potassium citrate
drospirenone and potassium citrate both increase serum potassium. Avoid or Use Alternate Drug.
- potassium phosphates, IV
drospirenone and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.
- protamine
estradiol decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- quinidine
quinidine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- repotrectinib
repotrectinib will decrease the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- rifabutin
rifabutin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of estradiol 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- spironolactone
drospirenone and spironolactone both increase serum potassium. Avoid or Use Alternate Drug.
drospirenone, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia. - triamterene
drospirenone and triamterene both increase serum potassium. Avoid or Use Alternate Drug.
drospirenone, triamterene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia. - tucatinib
tucatinib will increase the level or effect of estradiol 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.
Monitor Closely (309)
- acebutolol
acebutolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- aceclofenac
drospirenone and aceclofenac both increase serum potassium. Modify Therapy/Monitor Closely.
- acemetacin
drospirenone and acemetacin both increase serum potassium. Modify Therapy/Monitor Closely.
- albiglutide
estradiol decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estradiol may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
drospirenone decreases effects of albiglutide by passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients. - albuterol
drospirenone increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- amikacin
amikacin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- aldesleukin
aldesleukin increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
- amiodarone
amiodarone will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amobarbital
amobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- amoxicillin
amoxicillin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- apalutamide
apalutamide will decrease the level or effect of estradiol by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
- aprepitant
aprepitant will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- arformoterol
drospirenone increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- armodafinil
armodafinil will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- aspirin
drospirenone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.
- aspirin rectal
drospirenone and aspirin rectal both increase serum potassium. Modify Therapy/Monitor Closely.
- aspirin/citric acid/sodium bicarbonate
drospirenone and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Modify Therapy/Monitor Closely.
- atazanavir
atazanavir, estradiol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estradiol. Use alternatives if available.
atazanavir, drospirenone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of drospirenone. Use alternatives if available. - atenolol
atenolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- atorvastatin
atorvastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- atogepant
drospirenone will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- avapritinib
drospirenone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- axitinib
drospirenone increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- azithromycin
azithromycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
- aztreonam
aztreonam will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- benazepril
benazepril and drospirenone both increase serum potassium. Use Caution/Monitor.
- bendroflumethiazide
drospirenone increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- betaxolol
betaxolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- bisoprolol
bisoprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- bosentan
bosentan will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bosutinib
bosutinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- budesonide
budesonide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bumetanide
drospirenone increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- butabarbital
butabarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- canagliflozin
drospirenone and canagliflozin both increase serum potassium. Use Caution/Monitor.
- candesartan
candesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- cannabidiol
cannabidiol, estradiol. 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.
- captopril
captopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- carbamazepine
carbamazepine will decrease the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Advise patients to use alternative contraceptive method during coadministration; continue alternative contraception for 28 days after discontinuing therapy to ensure contraception reliability
- carbenoxolone
drospirenone increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- carvedilol
carvedilol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- cefaclor
cefaclor will decrease the level or effect of estradiol 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 estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefamandole
cefamandole will decrease the level or effect of estradiol 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 estradiol 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 estradiol 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 estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- cefpirome
cefpirome will decrease the level or effect of estradiol 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 estradiol 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 estradiol 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 estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- celecoxib
drospirenone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.
- celiprolol
celiprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- cenobamate
cenobamate will decrease the level or effect of estradiol 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 estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- ceritinib
ceritinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- chloramphenicol
chloramphenicol increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May increase side effects.
- chlorhexidine oral
chlorhexidine oral will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- chlorothiazide
drospirenone increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- chlorthalidone
drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- choline magnesium trisalicylate
drospirenone and choline magnesium trisalicylate both increase serum potassium. Modify Therapy/Monitor Closely.
- ciprofloxacin
ciprofloxacin will decrease the level or effect of estradiol 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 estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
clarithromycin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - clindamycin
clindamycin will decrease the level or effect of estradiol 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 drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clobazam is a weak CYP3A4 inducer; effectiveness of hormonal contraceptives may be diminished when given concurrently with clobazam. Additional non-hormonal forms of contraception are recommended.
- clotrimazole
clotrimazole will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- conivaptan
conivaptan will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cortisone
cortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclopenthiazide
drospirenone increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- cyclosporine
cyclosporine will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
cyclosporine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
drospirenone, cyclosporine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Monitor serum cyclosporine concentrations, and for signs and symptoms of renal and hepatic toxicity. - dabrafenib
dabrafenib will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- darunavir
darunavir will increase the level or effect of drospirenone 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.
- dapsone
dapsone will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- darifenacin
darifenacin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- darunavir
darunavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dasatinib
dasatinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- deferasirox
deferasirox will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- demeclocycline
demeclocycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- dexamethasone
dexamethasone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- DHEA, herbal
DHEA, herbal will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diclofenac
drospirenone and diclofenac both increase serum potassium. Modify Therapy/Monitor Closely.
- diflunisal
drospirenone and diflunisal both increase serum potassium. Modify Therapy/Monitor Closely.
- digoxin
drospirenone and digoxin both increase serum potassium. Modify Therapy/Monitor Closely.
- diltiazem
diltiazem will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- disopyramide
drospirenone increases effects of disopyramide by pharmacodynamic synergism. Use Caution/Monitor. Additive cardiovascular depression.
- dobutamine
drospirenone increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- dopexamine
drospirenone increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- doxycycline
doxycycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
dronedarone will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - efavirenz
efavirenz will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix will decrease the level or effect of estradiol 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.
- eliglustat
eliglustat increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- enalapril
enalapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- encorafenib
encorafenib, estradiol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- ephedrine
drospirenone increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- epinephrine
drospirenone increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- epinephrine racemic
drospirenone increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- eprosartan
eprosartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- ertapenem
ertapenem will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- erythromycin base
erythromycin base will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
erythromycin base will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - erythromycin ethylsuccinate
erythromycin ethylsuccinate will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
erythromycin ethylsuccinate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - erythromycin lactobionate
erythromycin lactobionate will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
erythromycin lactobionate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - erythromycin stearate
erythromycin stearate will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
erythromycin stearate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- esmolol
esmolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- ethacrynic acid
drospirenone increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- etodolac
drospirenone and etodolac both increase serum potassium. Modify Therapy/Monitor Closely.
- etravirine
etravirine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- exemestane
estradiol decreases effects of exemestane by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens or estrogen-containing products, including combined oral contraceptives, should not be given concomitantly with exemestane; these drugs could interfere with the pharmacologic action and efficacy of exemestane.
- exenatide injectable solution
estradiol, 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. .
drospirenone, 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
estradiol, 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.
drospirenone, 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fenbufen
drospirenone and fenbufen both increase serum potassium. Modify Therapy/Monitor Closely.
- felodipine
felodipine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fenoprofen
drospirenone and fenoprofen both increase serum potassium. Modify Therapy/Monitor Closely.
- fexinidazole
fexinidazole will increase the level or effect of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- finerenone
drospirenone 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.
drospirenone and finerenone both increase serum potassium. Modify Therapy/Monitor Closely. Finerenone dose adjustment based on current serum potassium concentration. Monitor serum potassium and adjust finerenone dose as described in the prescribing information as necessary. - fleroxacin
fleroxacin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- flibanserin
drospirenone 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fludrocortisone
fludrocortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- flurbiprofen
drospirenone and flurbiprofen both increase serum potassium. Modify Therapy/Monitor Closely.
- formoterol
drospirenone increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- fosamprenavir
fosamprenavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosaprepitant
fosaprepitant will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosfomycin
fosfomycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- fosinopril
fosinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- fosphenytoin
fosphenytoin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
fosphenytoin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - fostamatinib
fostamatinib will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- furosemide
drospirenone increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- gemifloxacin
gemifloxacin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- gentamicin
gentamicin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
drospirenone increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. - glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- hydrochlorothiazide
drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- grapefruit
grapefruit will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- griseofulvin
griseofulvin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- hemin
estradiol decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.
- hyaluronidase
estradiol 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.
- hydrocortisone
hydrocortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ibuprofen
drospirenone and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.
- ibuprofen IV
drospirenone and ibuprofen IV both increase serum potassium. Modify Therapy/Monitor Closely.
- iloperidone
iloperidone increases levels of estradiol 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.
- imidapril
imidapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- indapamide
drospirenone increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- indinavir
indinavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
indinavir will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - indomethacin
drospirenone and indomethacin both increase serum potassium. Modify Therapy/Monitor Closely.
- insulin degludec
estradiol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.
- insulin degludec/insulin aspart
estradiol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.
- insulin inhaled
estradiol decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.
- irbesartan
irbesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- isoproterenol
drospirenone increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- istradefylline
istradefylline will increase the level or effect of estradiol 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
itraconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - ivacaftor
drospirenone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
ivacaftor increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index. - juniper
juniper, drospirenone. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.
- ketoconazole
ketoconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ketoconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - ketoprofen
drospirenone and ketoprofen both increase serum potassium. Modify Therapy/Monitor Closely.
- ketorolac
drospirenone and ketorolac both increase serum potassium. Modify Therapy/Monitor Closely.
- ketorolac intranasal
drospirenone and ketorolac intranasal both increase serum potassium. Modify Therapy/Monitor Closely.
- labetalol
labetalol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- lamotrigine
estradiol decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.
drospirenone will decrease the level or effect of lamotrigine by increasing hepatic clearance. Use Caution/Monitor. Combination oral contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. - lapatinib
lapatinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
lapatinib will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - lemborexant
drospirenone 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 estradiol 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.
- letermovir
letermovir increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
drospirenone increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- levofloxacin
levofloxacin will decrease the level or effect of estradiol 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
levoketoconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - linezolid
linezolid will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- liraglutide
drospirenone decreases effects of liraglutide by passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
estradiol decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Estradiol may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients. - lisinopril
lisinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- lomitapide
lomitapide increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
- lomitapide
drospirenone increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- lonapegsomatropin
drospirenone 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.
drospirenone will decrease the level or effect of lonapegsomatropin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be required - lopinavir
lopinavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- loratadine
loratadine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lornoxicam
drospirenone and lornoxicam both increase serum potassium. Modify Therapy/Monitor Closely.
- losartan
losartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- lovastatin
lovastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lumefantrine
lumefantrine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- maraviroc
drospirenone 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mavacamten
drospirenone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.
- meclofenamate
drospirenone and meclofenamate both increase serum potassium. Modify Therapy/Monitor Closely.
- mefenamic acid
drospirenone and mefenamic acid both increase serum potassium. Modify Therapy/Monitor Closely.
- meloxicam
drospirenone and meloxicam both increase serum potassium. Modify Therapy/Monitor Closely.
- meropenem
meropenem will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- meropenem/vaborbactam
meropenem/vaborbactam will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- metaproterenol
drospirenone increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- metformin
estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. - methyclothiazide
drospirenone increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. .
- methylprednisolone
methylprednisolone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metolazone
drospirenone increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- metoprolol
metoprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- metronidazole
metronidazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
metronidazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - miconazole vaginal
miconazole vaginal will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- midazolam intranasal
drospirenone 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 will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
mifepristone decreases effects of drospirenone by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended. - minocycline
minocycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- moexipril
moexipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- mitotane
mitotane decreases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- moxifloxacin
moxifloxacin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- nabumetone
drospirenone and nabumetone both increase serum potassium. Modify Therapy/Monitor Closely.
- nadolol
nadolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- nafcillin
nafcillin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
nafcillin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - naproxen
drospirenone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.
- nebivolol
nebivolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- nefazodone
nefazodone will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nelfinavir
nelfinavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- neomycin PO
neomycin PO will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- nevirapine
nevirapine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nifedipine
nifedipine will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
nifedipine will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nilotinib
nilotinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
nilotinib will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nitrofurantoin
nitrofurantoin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- noni juice
drospirenone and noni juice both increase serum potassium. Use Caution/Monitor.
- norepinephrine
drospirenone increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- ofloxacin
ofloxacin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- olmesartan
olmesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- oxaprozin
drospirenone and oxaprozin both increase serum potassium. Modify Therapy/Monitor Closely.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- oxytetracycline
oxytetracycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- parecoxib
drospirenone and parecoxib both increase serum potassium. Modify Therapy/Monitor Closely.
- paromomycin
paromomycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- penbutolol
penbutolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- pentobarbital
pentobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- perindopril
perindopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- phenobarbital
phenobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenobarbital will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - phenytoin
phenytoin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - pindolol
pindolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- pirbuterol
drospirenone increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- piroxicam
drospirenone and piroxicam both increase serum potassium. Modify Therapy/Monitor Closely.
- pivmecillinam
pivmecillinam increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.
pivmecillinam will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. - ponatinib
ponatinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- potassium citrate/citric acid
drospirenone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.
- posaconazole
posaconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- potassium iodide
potassium iodide and drospirenone both increase serum potassium. Use Caution/Monitor.
- prednisone
prednisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- primidone
primidone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- propranolol
propranolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- quercetin
quercetin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- quinapril
quinapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- quinupristin/dalfopristin
quinupristin/dalfopristin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
quinupristin/dalfopristin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - ramipril
ramipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- ranolazine
ranolazine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ribociclib
ribociclib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ritonavir will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - roxithromycin
roxithromycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.
- rufinamide
rufinamide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- sacubitril/valsartan
sacubitril/valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- salicylates (non-asa)
drospirenone and salicylates (non-asa) both increase serum potassium. Modify Therapy/Monitor Closely.
- salmeterol
drospirenone increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- salsalate
drospirenone and salsalate both increase serum potassium. Modify Therapy/Monitor Closely.
- secobarbital
secobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- siltuximab
siltuximab, drospirenone. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.
- simvastatin
simvastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sirolimus
sirolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- somapacitan
estradiol 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.
drospirenone 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 - St John's Wort
St John's Wort will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- somatrogon
drospirenone 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
drospirenone 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
- sotalol
sotalol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- sparsentan
sparsentan and drospirenone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.
- stiripentol
stiripentol, estradiol. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.
- streptomycin
streptomycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- succinylcholine
drospirenone and succinylcholine both increase serum potassium. Modify Therapy/Monitor Closely.
- sulfadiazine
sulfadiazine will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- sulfamethoxazole
sulfamethoxazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- sulfasalazine
drospirenone and sulfasalazine both increase serum potassium. Modify Therapy/Monitor Closely.
- sulfisoxazole
sulfisoxazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- sulindac
drospirenone and sulindac both increase serum potassium. Modify Therapy/Monitor Closely.
- tacrolimus
tacrolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tazemetostat
drospirenone will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
tazemetostat will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tecovirimat
tecovirimat will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- telmisartan
telmisartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- teicoplanin
teicoplanin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- temocillin
temocillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.
temocillin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. - terbutaline
drospirenone increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- teriflunomide
teriflunomide decreases levels of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- tetracycline
tetracycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- ticarcillin
ticarcillin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
ticarcillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia. - tigecycline
tigecycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- timolol
timolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- tinidazole
drospirenone will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tobramycin
tobramycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- tolfenamic acid
drospirenone and tolfenamic acid both increase serum potassium. Modify Therapy/Monitor Closely.
- tolmetin
drospirenone and tolmetin both increase serum potassium. Modify Therapy/Monitor Closely.
- tolvaptan
tolvaptan will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
drospirenone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely. - topiramate
topiramate will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- torsemide
drospirenone increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- trandolapril
trandolapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.
- trazodone
trazodone will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- trimethoprim
trimethoprim will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- valoctocogene roxaparvovec
drospirenone 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
estradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency
- valsartan
valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.
- vancomycin
vancomycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- verapamil
verapamil will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
verapamil will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - voclosporin
voclosporin and drospirenone both increase serum potassium. Use Caution/Monitor.
- voriconazole
voriconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- warfarin
estradiol increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.
drospirenone increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. - xipamide
xipamide increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor.
- zafirlukast
zafirlukast will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (65)
- acetazolamide
acetazolamide will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- agrimony
agrimony increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- amitriptyline
estradiol, 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
estradiol, 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 estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- androstenedione
androstenedione increases effects of estradiol by pharmacodynamic synergism. Minor/Significance Unknown.
- birch
birch increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- boron
boron increases levels of estradiol by altering metabolism. Minor/Significance Unknown.
- brimonidine
brimonidine increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- cadexomer iodine
cadexomer iodine, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.
- calcium acetate
drospirenone decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.
- calcium carbonate
drospirenone decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.
- calcium chloride
drospirenone decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.
- calcium citrate
drospirenone decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.
- calcium gluconate
drospirenone decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.
- clomipramine
estradiol, clomipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- cornsilk
cornsilk increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- cyanocobalamin
estradiol decreases levels of cyanocobalamin by altering metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- desipramine
estradiol, 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
estradiol, 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
estradiol, doxepin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- enasidenib
enasidenib, drospirenone. 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.
- epoprostenol
epoprostenol increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.
- folic acid
estradiol decreases levels of folic acid by altering metabolism. Minor/Significance Unknown.
- forskolin
forskolin increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- goldenrod
goldenrod increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- imipramine
estradiol, imipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- iodinated glycerol
iodinated glycerol, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.
- iodine
iodine, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.
- isoniazid
isoniazid will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- L-methylfolate
estradiol decreases levels of L-methylfolate by altering metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lofepramine
estradiol, 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
drospirenone increases levels of magnesium chloride by decreasing renal clearance. Minor/Significance Unknown.
estradiol decreases levels of magnesium chloride by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage. - magnesium citrate
drospirenone increases levels of magnesium citrate by decreasing renal clearance. Minor/Significance Unknown.
estradiol decreases levels of magnesium citrate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage. - magnesium hydroxide
drospirenone increases levels of magnesium hydroxide by decreasing renal clearance. Minor/Significance Unknown.
estradiol decreases levels of magnesium hydroxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage. - magnesium oxide
drospirenone increases levels of magnesium oxide by decreasing renal clearance. Minor/Significance Unknown.
estradiol decreases levels of magnesium oxide by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage. - magnesium sulfate
drospirenone increases levels of magnesium sulfate by decreasing renal clearance. Minor/Significance Unknown.
estradiol decreases levels of magnesium sulfate by Other (see comment). Minor/Significance Unknown. Comment: Magnesium shifted from blood to tissue storage. - maitake
maitake increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- maprotiline
estradiol, 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
estradiol decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.
- minoxidil
drospirenone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.
- mycophenolate
mycophenolate decreases effects of estradiol by unknown mechanism. Minor/Significance Unknown. Clinical significance unclear.
- nortriptyline
estradiol, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- octacosanol
octacosanol increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- phytoestrogens
phytoestrogens decreases effects of estradiol by pharmacodynamic antagonism. Minor/Significance Unknown.
- pleurisy root
pleurisy root decreases effects of estradiol by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.
- protriptyline
estradiol, 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
estradiol decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.
- pyridoxine (Antidote)
estradiol decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.
- reishi
reishi increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- ropinirole
estradiol increases levels of ropinirole by unspecified interaction mechanism. Minor/Significance Unknown.
- rose hips
estradiol decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.
- ruxolitinib
drospirenone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
drospirenone will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- shepherd's purse
shepherd's purse, drospirenone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
- sulfadiazine
drospirenone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.
- sulfamethoxazole
drospirenone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
drospirenone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown. - sulfisoxazole
drospirenone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
- tizanidine
tizanidine increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.
- trazodone
estradiol, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.
- treprostinil
treprostinil increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.
- trimethoprim
drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
- trimipramine
estradiol, 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
>10%
Breast pain (19%)
Upper respiratory infection (19%)
Abdominal pain (11%)
1-10%
Edema
Peripheral edema
Headache
Accidental injury, back pain, pain in extremity
Endometrial disorder
Leukorrhea
Vaginal hemorrhage
Abdominal enlargement
Flu syndrome
Sinusitis
Warnings
Cardiovascular risks
Estrogens with and without progestins should not be used to prevent cardiovascular disease
Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism (PE), and deep vein thrombosis (DVT) in postmenopausal women (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
Dementia risks
Estrogens with and without progestins should not be used to prevent dementia
Women's Health Initiative Memory Study (WHIMS), substudy of WHI study, reported increased risk of developing probable dementia in postmenopausal women ≥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
Unknown whether these findings apply to younger postmenopausal women
Breast cancer
The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer; prescribe estrogens with or without progestins at the lowest doses and for the shortest duration
Increased risk of endometrial cancer
Close clinical surveillance of all women taking estrogens is important
Risk of endometrial cancer in women with a uterus increases with use of unopposed estrogens; adding progestin to estrogen therapy may reduce risk of endometrial hyperplasia, a precursor to endometrial cancer
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
Contraindications
Hypersensitivity
Undiagnosed abnormal genital bleeding
Known, suspected, or history of cancer of the breast
Known or suspected estrogen-dependent neoplasia
Active DVT, PE, or a history of these conditions
Active arterial thromboembolic disease (for example, stroke and MI), or history of these conditions
Renal impairment
Known liver impairment or disease
Adrenal insufficiency
Known or suspected pregnancy
Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Known anaphylactic reaction, angioedema, or hypersensitivity
Cautions
Use caution in bone mineral density changes, current/history of depression, DM, HTN, hyperlipidemia, obesity, endometriosis, family history of breast cancer, DVT/PE, smoking
Discontinue if the following develop: jaundice, visual problems, 4-6 wk before major surgery, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression
Increased risk of post-op thromboembolic complications, arterial/venous thromboembolic disorder, hyperkalemia, exacerbation of endometriosis
Do not use with conditions that predispose to hyperkalemia
Conditions exacerbated by fluid retention (eg, asthma, migraine, cardiac/renal dysfunction, epilepsy)
Patients on warfarin/oral anticoagulants: oestrogens increase thromboembolic risk; increase in anticoagulant dose may be warranted
History of migraine with aura
Cholelithiasis
Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema
Consider topical vaginal products when used solely for vulvovaginal atrophy
Increased risk of ovarian cancer reported in women who used hormonal therapy for menopausal symptoms
Manage appropriately risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus)
A 2 to 4-fold increase in risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens reported
Retinal vascular thrombosis 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 discontinued
There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance
In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications
Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue medication
Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range
Use caution in individuals with severe hypocalcemia
Pregnancy & Lactation
Pregnancy Category: contraindicated in pregnancy
Lactation: enters breast milk/not recommended
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
Estradiol: Endogenous estrogen; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues. Estrogen replacement reduces elevated levels of estrogen and progesterone LH and FSH in postmenopausal women
Drospirenone: Progestin; spironolactone analog with antimineralocorticoid and antiandrogenic activity
Pharmacokinetics
Half-Life elimination: 36-42 hr (drospirenone)
Vd: 4.2 L/kg (drospirenone)
Metabolism: Hepatic
Bioavailability: 76-85% (drosperidone)
Metabolites: Inactive
Excretion: Urine, feces
Peak plasma time
- Drospirenone: 1 hr
- Estradiol: 6-8 hr
Peak plasma concentration
- Drospirenone: 13-24 ng/mL
- Estradiol: 34-54 pg/mL
Protein bound
- Drospirenone: 97% bound to serum proteins (not SHBG or corticosteroid binding globulin)
- Estradiol: 98% (37% to globulin and 61% to albumin)
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Formulary
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