drospirenone/estradiol (Rx)

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

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.

• acebutolol

  Monitor Closely (1)acebutolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• aceclofenac

  Monitor Closely (1)drospirenone and aceclofenac both increase serum potassium. Modify Therapy/Monitor Closely.

• acemetacin

  Monitor Closely (1)drospirenone and acemetacin both increase serum potassium. Modify Therapy/Monitor Closely.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  Minor (1)agrimony increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (2)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

  Monitor Closely (1)drospirenone increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• aldesleukin

  Monitor Closely (1)aldesleukin increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• amikacin

  Monitor Closely (1)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.

• amiloride

  Serious - Use Alternative (2)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.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amitriptyline

  Minor (1)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.

• amobarbital

  Monitor Closely (1)amobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amoxapine

  Minor (1)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.

• amoxicillin

  Monitor Closely (1)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.

• anastrozole

  Serious - Use Alternative (1)estradiol decreases effects of anastrozole by pharmacodynamic antagonism. Contraindicated. Estrogen may diminish the pharmacologic action of anastrozole. Coadministration not recommended.Minor (1)anastrozole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• androstenedione

  Minor (1)androstenedione increases effects of estradiol by pharmacodynamic synergism. Minor/Significance Unknown.

• antithrombin alfa

  Serious - Use Alternative (1)estradiol decreases effects of antithrombin alfa by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• antithrombin III

  Serious - Use Alternative (1)estradiol decreases effects of antithrombin III by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• apalutamide

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (1)drospirenone increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• argatroban

  Serious - Use Alternative (1)estradiol decreases effects of argatroban by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• armodafinil

  Monitor Closely (1)armodafinil will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aspirin

  Monitor Closely (1)drospirenone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• aspirin rectal

  Monitor Closely (1)drospirenone and aspirin rectal both increase serum potassium. Modify Therapy/Monitor Closely.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)drospirenone and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Modify Therapy/Monitor Closely.

• atazanavir

  Monitor Closely (2)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

  Monitor Closely (1)atenolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• atogepant

  Monitor Closely (1)drospirenone will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)atorvastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avapritinib

  Monitor Closely (1)drospirenone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axitinib

  Monitor Closely (1)drospirenone increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azithromycin

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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. Serious - Use Alternative (1)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

  Serious - Use Alternative (1)estradiol decreases effects of bemiparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• benazepril

  Monitor Closely (1)benazepril and drospirenone both increase serum potassium. Use Caution/Monitor.

• bendroflumethiazide

  Monitor Closely (1)drospirenone increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• betaxolol

  Monitor Closely (1)betaxolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• birch

  Minor (1)birch increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

  Monitor Closely (1)bisoprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• bivalirudin

  Serious - Use Alternative (1)estradiol decreases effects of bivalirudin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• boron

  Minor (1)boron increases levels of estradiol by altering metabolism. Minor/Significance Unknown.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosutinib

  Monitor Closely (1)bosutinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• brimonidine

  Minor (1)brimonidine increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  Monitor Closely (1)budesonide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bumetanide

  Monitor Closely (1)drospirenone increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• butabarbital

  Monitor Closely (1)butabarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cadexomer iodine

  Minor (1)cadexomer iodine, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• calaspargase pegol

  Serious - Use Alternative (1)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.

• calcium acetate

  Minor (1)drospirenone decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  Minor (1)drospirenone decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  Minor (1)drospirenone decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  Minor (1)drospirenone decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  Minor (1)drospirenone decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• canagliflozin

  Monitor Closely (1)drospirenone and canagliflozin both increase serum potassium. Use Caution/Monitor.

• candesartan

  Monitor Closely (1)candesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• cannabidiol

  Monitor Closely (1)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

  Monitor Closely (1)captopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• carbamazepine

  Monitor Closely (1)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 Serious - Use Alternative (1)carbamazepine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• carbenoxolone

  Monitor Closely (1)drospirenone increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carvedilol

  Monitor Closely (1)carvedilol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• cefaclor

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• celiprolol

  Monitor Closely (1)celiprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• cenobamate

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)ceritinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloramphenicol

  Monitor Closely (1)chloramphenicol increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May increase side effects.

• chlorhexidine oral

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chlorthalidone

  Monitor Closely (1)drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• choline magnesium trisalicylate

  Monitor Closely (1)drospirenone and choline magnesium trisalicylate both increase serum potassium. Modify Therapy/Monitor Closely.

• cimetidine

  Serious - Use Alternative (1)cimetidine will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ciprofloxacin

  Monitor Closely (1)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

  Monitor Closely (2)clarithromycin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)clarithromycin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clindamycin

  Monitor Closely (1)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

  Monitor Closely (1)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.

• clomipramine

  Minor (1)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.

• clotrimazole

  Monitor Closely (1)clotrimazole will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cornsilk

  Minor (1)cornsilk increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• cortisone

  Monitor Closely (1)cortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crofelemer

  Monitor Closely (1)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.

• cyanocobalamin

  Minor (1)estradiol decreases levels of cyanocobalamin by altering metabolism. Minor/Significance Unknown.

• cyclopenthiazide

  Monitor Closely (1)drospirenone increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (3)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

  Monitor Closely (1)dabrafenib will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dalteparin

  Serious - Use Alternative (1)estradiol decreases effects of dalteparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• dapsone

  Monitor Closely (1)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

  Monitor Closely (1)darifenacin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (2)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.
  
  darunavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dasatinib

  Monitor Closely (1)dasatinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• demeclocycline

  Monitor Closely (1)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.

• desipramine

  Minor (1)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.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• DHEA, herbal

  Monitor Closely (1)DHEA, herbal will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diclofenac

  Monitor Closely (1)drospirenone and diclofenac both increase serum potassium. Modify Therapy/Monitor Closely.

• diflunisal

  Monitor Closely (1)drospirenone and diflunisal both increase serum potassium. Modify Therapy/Monitor Closely.

• digoxin

  Monitor Closely (1)drospirenone and digoxin both increase serum potassium. Modify Therapy/Monitor Closely.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  Monitor Closely (1)drospirenone increases effects of disopyramide by pharmacodynamic synergism. Use Caution/Monitor. Additive cardiovascular depression.

• dobutamine

  Monitor Closely (1)drospirenone increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• dopexamine

  Monitor Closely (1)drospirenone increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• dosulepin

  Minor (1)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

  Minor (1)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.

• doxycycline

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)efavirenz will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)enalapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• enasidenib

  Minor (1)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.

• encorafenib

  Monitor Closely (1)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.

• enoxaparin

  Serious - Use Alternative (1)estradiol decreases effects of enoxaparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• enzalutamide

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (1)drospirenone increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• epinephrine

  Monitor Closely (1)drospirenone increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• epinephrine racemic

  Monitor Closely (1)drospirenone increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• eplerenone

  Serious - Use Alternative (1)drospirenone, eplerenone. Mechanism: pharmacodynamic synergism. Contraindicated. Hyperkalemia.

• epoprostenol

  Minor (1)epoprostenol increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• eprosartan

  Monitor Closely (1)eprosartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• erdafitinib

  Serious - Use Alternative (1)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.

• ertapenem

  Monitor Closely (1)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

  Monitor Closely (2)erythromycin base will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)erythromycin base will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (2)erythromycin ethylsuccinate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (2)erythromycin lactobionate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (2)erythromycin stearate will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• esmolol

  Monitor Closely (1)esmolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• ethacrynic acid

  Monitor Closely (1)drospirenone increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• etodolac

  Monitor Closely (1)drospirenone and etodolac both increase serum potassium. Modify Therapy/Monitor Closely.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• exemestane

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• felodipine

  Monitor Closely (1)felodipine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fenbufen

  Monitor Closely (1)drospirenone and fenbufen both increase serum potassium. Modify Therapy/Monitor Closely.

• fenoprofen

  Monitor Closely (1)drospirenone and fenoprofen both increase serum potassium. Modify Therapy/Monitor Closely.

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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.

• fezolinetant

  Contraindicated (1)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

• finerenone

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)fluconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fludrocortisone

  Monitor Closely (1)fludrocortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flurbiprofen

  Monitor Closely (1)drospirenone and flurbiprofen both increase serum potassium. Modify Therapy/Monitor Closely.

• folic acid

  Minor (1)estradiol decreases levels of folic acid by altering metabolism. Minor/Significance Unknown.

• fondaparinux

  Serious - Use Alternative (1)estradiol decreases effects of fondaparinux by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• formoterol

  Monitor Closely (1)drospirenone increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• forskolin

  Minor (1)forskolin increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosfomycin

  Monitor Closely (1)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

  Monitor Closely (1)fosinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• fosphenytoin

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• gemifloxacin

  Monitor Closely (1)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

  Monitor Closely (2)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.

• givosiran

  Serious - Use Alternative (1)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.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• goldenrod

  Minor (1)goldenrod increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• griseofulvin

  Monitor Closely (1)griseofulvin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hemin

  Monitor Closely (1)estradiol decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• heparin

  Serious - Use Alternative (1)estradiol decreases effects of heparin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• hyaluronidase

  Monitor Closely (1)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.

• hydrochlorothiazide

  Monitor Closely (1)drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• hydrocortisone

  Monitor Closely (1)hydrocortisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ibuprofen

  Monitor Closely (1)drospirenone and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.

• ibuprofen IV

  Monitor Closely (1)drospirenone and ibuprofen IV both increase serum potassium. Modify Therapy/Monitor Closely.

• idelalisib

  Serious - Use Alternative (1)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

• iloperidone

  Monitor Closely (1)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

  Monitor Closely (1)imidapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• imipramine

  Minor (1)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.

• indapamide

  Monitor Closely (1)drospirenone increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• indinavir

  Monitor Closely (2)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

  Monitor Closely (1)drospirenone and indomethacin both increase serum potassium. Modify Therapy/Monitor Closely.

• insulin degludec

  Monitor Closely (1)estradiol decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

• insulin degludec/insulin aspart

  Monitor Closely (1)estradiol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

• insulin inhaled

  Monitor Closely (1)estradiol decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

• iodinated glycerol

  Minor (1)iodinated glycerol, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• iodine

  Minor (1)iodine, drospirenone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• irbesartan

  Monitor Closely (1)irbesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• isavuconazonium sulfate

  Serious - Use Alternative (1)isavuconazonium sulfate will increase the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isoniazid

  Minor (1)isoniazid will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (1)drospirenone increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• istradefylline

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (2)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.

• ivosidenib

  Serious - Use Alternative (1)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.

• juniper

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)drospirenone and ketoprofen both increase serum potassium. Modify Therapy/Monitor Closely.

• ketorolac

  Monitor Closely (1)drospirenone and ketorolac both increase serum potassium. Modify Therapy/Monitor Closely.

• ketorolac intranasal

  Monitor Closely (1)drospirenone and ketorolac intranasal both increase serum potassium. Modify Therapy/Monitor Closely.

• L-methylfolate

  Minor (1)estradiol decreases levels of L-methylfolate by altering metabolism. Minor/Significance Unknown.

• labetalol

  Monitor Closely (1)labetalol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• lamotrigine

  Monitor Closely (2)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.
  
  estradiol decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.

• lapatinib

  Monitor Closely (2)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.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lemborexant

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)letermovir increases levels of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (1)drospirenone increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• levofloxacin

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)lisinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• lofepramine

  Minor (1)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.

• lomitapide

  Monitor Closely (2)lomitapide increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
  
  drospirenone increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)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.

• lonapegsomatropin

  Monitor Closely (2)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

  Monitor Closely (1)lopinavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loratadine

  Monitor Closely (1)loratadine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lornoxicam

  Monitor Closely (1)drospirenone and lornoxicam both increase serum potassium. Modify Therapy/Monitor Closely.

• losartan

  Monitor Closely (1)losartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• lovastatin

  Monitor Closely (1)lovastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lumefantrine

  Monitor Closely (1)lumefantrine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• magnesium chloride

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (1)maitake increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• maprotiline

  Minor (1)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.

• maraviroc

  Monitor Closely (1)drospirenone increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.

• marijuana

  Monitor Closely (1)marijuana will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mavacamten

  Monitor Closely (1)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. Serious - Use Alternative (1)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.

• meclofenamate

  Monitor Closely (1)drospirenone and meclofenamate both increase serum potassium. Modify Therapy/Monitor Closely.

• mefenamic acid

  Monitor Closely (1)drospirenone and mefenamic acid both increase serum potassium. Modify Therapy/Monitor Closely.

• meloxicam

  Monitor Closely (1)drospirenone and meloxicam both increase serum potassium. Modify Therapy/Monitor Closely.

• meropenem

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• metformin

  Monitor Closely (2)estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methyclothiazide

  Monitor Closely (1)drospirenone increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. .

• methylprednisolone

  Monitor Closely (1)methylprednisolone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metolazone

  Monitor Closely (1)drospirenone increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• metoprolol

  Monitor Closely (1)metoprolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• metronidazole

  Monitor Closely (2)metronidazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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.

• metyrapone

  Minor (1)estradiol decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• miconazole vaginal

  Monitor Closely (1)miconazole vaginal will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)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.

• minoxidil

  Minor (1)drospirenone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

• mitotane

  Monitor Closely (1)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.

• mobocertinib

  Serious - Use Alternative (1)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.

• moexipril

  Monitor Closely (1)moexipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• moxifloxacin

  Monitor Closely (1)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.

• mycophenolate

  Minor (1)mycophenolate decreases effects of estradiol by unknown mechanism. Minor/Significance Unknown. Clinical significance unclear.

• nabumetone

  Monitor Closely (1)drospirenone and nabumetone both increase serum potassium. Modify Therapy/Monitor Closely.

• nadolol

  Monitor Closely (1)nadolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• nafcillin

  Monitor Closely (2)nafcillin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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.

• naproxen

  Monitor Closely (1)drospirenone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.

• nebivolol

  Monitor Closely (1)nebivolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• nefazodone

  Monitor Closely (1)nefazodone will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  Monitor Closely (1)nelfinavir will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• neomycin PO

  Monitor Closely (1)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

  Monitor Closely (1)nevirapine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone and noni juice both increase serum potassium. Use Caution/Monitor.

• norepinephrine

  Monitor Closely (1)drospirenone increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• nortriptyline

  Minor (1)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

  Minor (1)octacosanol increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

  Monitor Closely (1)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

  Monitor Closely (1)olmesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• omaveloxolone

  Serious - Use Alternative (1)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.

• ospemifene

  Contraindicated (1)ospemifene, estradiol. Either increases effects of the other by pharmacodynamic synergism. Contraindicated.

• oxaprozin

  Monitor Closely (1)drospirenone and oxaprozin both increase serum potassium. Modify Therapy/Monitor Closely.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxytetracycline

  Monitor Closely (1)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.

• pacritinib

  Serious - Use Alternative (1)estradiol will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• parecoxib

  Monitor Closely (1)drospirenone and parecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• paromomycin

  Monitor Closely (1)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

  Monitor Closely (1)penbutolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• pentobarbital

  Monitor Closely (1)pentobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• perindopril

  Monitor Closely (1)perindopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• phenindione

  Serious - Use Alternative (1)estradiol decreases effects of phenindione by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• phenobarbital

  Monitor Closely (2)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

  Monitor Closely (2)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.

• phytoestrogens

  Minor (1)phytoestrogens decreases effects of estradiol by pharmacodynamic antagonism. Minor/Significance Unknown.

• pindolol

  Monitor Closely (1)pindolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• pirbuterol

  Monitor Closely (1)drospirenone increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• piroxicam

  Monitor Closely (1)drospirenone and piroxicam both increase serum potassium. Modify Therapy/Monitor Closely.

• pivmecillinam

  Monitor Closely (2)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.

• pleurisy root

  Minor (1)pleurisy root decreases effects of estradiol by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• ponatinib

  Monitor Closely (1)ponatinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• posaconazole

  Monitor Closely (1)posaconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• potassium acid phosphate

  Serious - Use Alternative (1)drospirenone and potassium acid phosphate both increase serum potassium. Avoid or Use Alternate Drug.

• potassium chloride

  Serious - Use Alternative (1)drospirenone and potassium chloride both increase serum potassium. Avoid or Use Alternate Drug.

• potassium citrate

  Serious - Use Alternative (1)drospirenone and potassium citrate both increase serum potassium. Avoid or Use Alternate Drug.

• potassium citrate/citric acid

  Monitor Closely (1)drospirenone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

• potassium iodide

  Monitor Closely (1)potassium iodide and drospirenone both increase serum potassium. Use Caution/Monitor.

• potassium phosphates, IV

  Serious - Use Alternative (1)drospirenone and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

• prednisone

  Monitor Closely (1)prednisone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primidone

  Monitor Closely (1)primidone will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• propranolol

  Monitor Closely (1)propranolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• protamine

  Serious - Use Alternative (1)estradiol decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

• protriptyline

  Minor (1)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

  Minor (1)estradiol decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.

• pyridoxine (Antidote)

  Minor (1)estradiol decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.

• quercetin

  Monitor Closely (1)quercetin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)quinapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• quinidine

  Serious - Use Alternative (1)quinidine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinupristin/dalfopristin

  Monitor Closely (2)quinupristin/dalfopristin will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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.

• ramipril

  Monitor Closely (1)ramipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• ranolazine

  Monitor Closely (1)ranolazine will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• reishi

  Minor (1)reishi increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• repotrectinib

  Serious - Use Alternative (1)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.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)rifampin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ritonavir

  Monitor Closely (2)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.

• ropinirole

  Minor (1)estradiol increases levels of ropinirole by unspecified interaction mechanism. Minor/Significance Unknown.

• rose hips

  Minor (1)estradiol decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

• roxithromycin

  Monitor Closely (1)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

  Monitor Closely (1)rufinamide will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib

  Minor (1)drospirenone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)drospirenone will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sacubitril/valsartan

  Monitor Closely (1)sacubitril/valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• salicylates (non-asa)

  Monitor Closely (1)drospirenone and salicylates (non-asa) both increase serum potassium. Modify Therapy/Monitor Closely.

• salmeterol

  Monitor Closely (1)drospirenone increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• salsalate

  Monitor Closely (1)drospirenone and salsalate both increase serum potassium. Modify Therapy/Monitor Closely.

• secobarbital

  Monitor Closely (1)secobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• shepherd's purse

  Minor (1)shepherd's purse, drospirenone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• siltuximab

  Monitor Closely (1)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

  Monitor Closely (1)simvastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sirolimus

  Monitor Closely (1)sirolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• somapacitan

  Monitor Closely (2)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

• somatrogon

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)sotalol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• sparsentan

  Monitor Closely (1)sparsentan and drospirenone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

• spironolactone

  Serious - Use Alternative (2)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.

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone and succinylcholine both increase serum potassium. Modify Therapy/Monitor Closely.

• sulfadiazine

  Monitor Closely (1)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.Minor (1)drospirenone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Monitor Closely (1)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.Minor (2)drospirenone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  drospirenone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

• sulfasalazine

  Monitor Closely (1)drospirenone and sulfasalazine both increase serum potassium. Modify Therapy/Monitor Closely.

• sulfisoxazole

  Monitor Closely (1)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.Minor (1)drospirenone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (1)drospirenone and sulindac both increase serum potassium. Modify Therapy/Monitor Closely.

• tacrolimus

  Monitor Closely (1)tacrolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tazemetostat

  Monitor Closely (2)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

  Monitor Closely (1)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.

• teicoplanin

  Monitor Closely (1)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.

• telmisartan

  Monitor Closely (1)telmisartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• temocillin

  Monitor Closely (2)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

  Monitor Closely (1)drospirenone increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetracycline

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)timolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• tinidazole

  Monitor Closely (1)drospirenone will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tizanidine

  Minor (1)tizanidine increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tobramycin

  Monitor Closely (1)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

  Monitor Closely (1)drospirenone and tolfenamic acid both increase serum potassium. Modify Therapy/Monitor Closely.

• tolmetin

  Monitor Closely (1)drospirenone and tolmetin both increase serum potassium. Modify Therapy/Monitor Closely.

• tolvaptan

  Monitor Closely (2)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

  Monitor Closely (1)topiramate will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• torsemide

  Monitor Closely (1)drospirenone increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• trandolapril

  Monitor Closely (1)trandolapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• trazodone

  Monitor Closely (1)trazodone will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)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

  Minor (1)treprostinil increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

• triamterene

  Serious - Use Alternative (2)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.

• trimethoprim

  Monitor Closely (1)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.Minor (1)drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

• trimipramine

  Minor (1)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.

• tucatinib

  Serious - Use Alternative (1)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.

• valoctocogene roxaparvovec

  Monitor Closely (1)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

  Monitor Closely (1)estradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency

• valsartan

  Monitor Closely (1)valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

• vancomycin

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)voclosporin and drospirenone both increase serum potassium. Use Caution/Monitor.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (2)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

  Monitor Closely (1)xipamide increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor.

• zafirlukast

  Monitor Closely (1)zafirlukast will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.