drospirenone/estradiol (Rx)

Brand and Other Names:Angeliq

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

drospirenone/estradiol

tablet

  • 0.25mg/0.5mg
  • 0.5mg/1mg

Hormone Replacement Therapy

1 tablet PO daily

Use the lowest dose that will control symptoms

Renal Impairment

Do not administer

Hepatic Impairment

Do not administer

Other Indications & Uses

Hormone replacement therapy for women with intact uterus: Treatment of menopause-associated hot flashes and vulvar/vaginal atrophy

Safety and efficacy not established

Hormone replacement therapy

1 tablet PO daily

Use the lowest dose that will control symptoms

Next:

Interactions

Interaction Checker

and drospirenone/estradiol

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            Contraindicated (1)

            • fezolinetant

              drospirenone 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

            Serious - Use Alternative (16)

            • 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.

            • 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.

            • 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.

            • eplerenone

              drospirenone, eplerenone. Mechanism: pharmacodynamic synergism. Contraindicated. Hyperkalemia.

            • 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.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • 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.

            • 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.

            • 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.

            Monitor Closely (142)

            • 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

              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.

            • aldesleukin

              aldesleukin increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • arformoterol

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

            • 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, 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.

            • 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.

            • 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.

            • bumetanide

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

            • canagliflozin

              drospirenone and canagliflozin both increase serum potassium. Use Caution/Monitor.

            • candesartan

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

            • 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.

            • celecoxib

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

            • celiprolol

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

            • 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.

            • 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.

            • cyclopenthiazide

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

            • cyclosporine

              drospirenone, cyclosporine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Monitor serum cyclosporine concentrations, and for signs and symptoms of renal and hepatic toxicity.

            • 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.

            • 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.

            • 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.

            • enalapril

              enalapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • 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.

            • 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.

            • exenatide injectable solution

              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

              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.

            • fenbufen

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

            • fenoprofen

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

            • 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.

            • 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.

            • 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.

            • fosinopril

              fosinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • furosemide

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

            • gentamicin

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

            • hydrochlorothiazide

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

            • 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.

            • 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.

            • indomethacin

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

            • 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.

            • ivacaftor

              drospirenone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • 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.

            • 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

              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.

            • 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.

            • levalbuterol

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

            • 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.

            • lisinopril

              lisinopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • 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.

            • lornoxicam

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

            • losartan

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

            • maraviroc

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

            • 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.

            • metaproterenol

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

            • metformin

              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. .

            • 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.

            • 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 decreases effects of drospirenone by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.

            • moexipril

              moexipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • nabumetone

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

            • nadolol

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

            • naproxen

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

            • nebivolol

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

            • 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.

            • olmesartan

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

            • oxaprozin

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

            • parecoxib

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

            • penbutolol

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

            • perindopril

              perindopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • 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.

            • potassium citrate/citric acid

              drospirenone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

            • potassium iodide

              potassium iodide and drospirenone both increase serum potassium. Use Caution/Monitor.

            • propranolol

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

            • quinapril

              quinapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • ramipril

              ramipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • 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.

            • 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.

            • 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.

            • succinylcholine

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

            • sulfasalazine

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

            • sulindac

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

            • tazemetostat

              drospirenone will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • telmisartan

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

            • temocillin

              temocillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

            • terbutaline

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

            • ticarcillin

              ticarcillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

            • 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.

            • 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

              drospirenone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.

            • 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.

            • valsartan

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

            • voclosporin

              voclosporin and drospirenone both increase serum potassium. Use Caution/Monitor.

            • warfarin

              drospirenone increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

            • xipamide

              xipamide increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor.

            Minor (34)

            • agrimony

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

            • birch

              birch increases effects of drospirenone by pharmacodynamic synergism. 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.

            • cornsilk

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

            • 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.

            • forskolin

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

            • goldenrod

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

            • iodinated glycerol

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

            • iodine

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

            • magnesium chloride

              drospirenone increases levels of magnesium chloride by decreasing renal clearance. Minor/Significance Unknown.

            • magnesium citrate

              drospirenone increases levels of magnesium citrate by decreasing renal clearance. Minor/Significance Unknown.

            • magnesium hydroxide

              drospirenone increases levels of magnesium hydroxide by decreasing renal clearance. Minor/Significance Unknown.

            • magnesium oxide

              drospirenone increases levels of magnesium oxide by decreasing renal clearance. Minor/Significance Unknown.

            • magnesium sulfate

              drospirenone increases levels of magnesium sulfate by decreasing renal clearance. Minor/Significance Unknown.

            • maitake

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

            • minoxidil

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

            • octacosanol

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

            • reishi

              reishi increases effects of drospirenone by pharmacodynamic synergism. 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.

            • treprostinil

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

            • trimethoprim

              drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

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            Adverse Effects

            >10%

            Breast pain (19%)

            Upper respiratory infection (19%)

            Abdominal pain (11%)

            1-10%

            Edema

            Peripheral edema

            Headache

            Accidental injury, back pain, pain in extremity

            Endometrial disorder

            Leukorrhea

            Vaginal hemorrhage

            Abdominal enlargement

            Flu syndrome

            Sinusitis

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            Warnings

            Contraindications

            Hypersensitivity

            Undiagnosed abnormal genital bleeding

            Known, suspected, or history of cancer of the breast

            Known or suspected estrogen-dependent neoplasia

            Active DVT, PE, or a history of these conditions

            Active arterial thromboembolic disease (for example, stroke and MI), or history of these conditions

            Renal impairment

            Known liver impairment or disease

            Adrenal insufficiency

            Known or suspected pregnancy

            Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

            Known anaphylactic reaction, angioedema, or hypersensitivity

            Cautions

            Use caution in bone mineral density changes, current/history of depression, DM, HTN, hyperlipidemia, obesity, endometriosis, family history of breast cancer, DVT/PE, smoking

            Discontinue if the following develop: jaundice, visual problems, 4-6 wk before major surgery, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression

            Increased risk of post-op thromboembolic complications, arterial/venous thromboembolic disorder, hyperkalemia, exacerbation of endometriosis

            Do not use with conditions that predispose to hyperkalemia

            Conditions exacerbated by fluid retention (eg, asthma, migraine, cardiac/renal dysfunction, epilepsy)

            Patients on warfarin/oral anticoagulants: oestrogens increase thromboembolic risk; increase in anticoagulant dose may be warranted

            History of migraine with aura

            Cholelithiasis

            Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema

            Consider topical vaginal products when used solely for vulvovaginal atrophy

            Increased risk of ovarian cancer reported in women who used hormonal therapy for menopausal symptoms

            Manage appropriately risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus)

            A 2 to 4-fold increase in risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens reported

            Retinal vascular thrombosis reported in patients receiving estrogens; discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if examination reveals papilledema or retinal vascular lesions, estrogens should be discontinued

            There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance

            In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications

            Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue medication

            Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range

            Use caution in individuals with severe hypocalcemia

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            Pregnancy & Lactation

            Pregnancy Category: contraindicated in pregnancy

            Lactation: enters breast milk/not recommended

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Estradiol: Endogenous estrogen; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues. Estrogen replacement reduces elevated levels of estrogen and progesterone LH and FSH in postmenopausal women

            Drospirenone: Progestin; spironolactone analog with antimineralocorticoid and antiandrogenic activity

            Pharmacokinetics

            Half-Life elimination: 36-42 hr (drospirenone)

            Vd: 4.2 L/kg (drospirenone)

            Metabolism: Hepatic

            Bioavailability: 76-85% (drosperidone)

            Metabolites: Inactive

            Excretion: Urine, feces

            Peak plasma time

            • Drospirenone: 1 hr
            • Estradiol: 6-8 hr

            Peak plasma concentration

            • Drospirenone: 13-24 ng/mL
            • Estradiol: 34-54 pg/mL

            Protein bound

            • Drospirenone: 97% bound to serum proteins (not SHBG or corticosteroid binding globulin)
            • Estradiol: 98% (37% to globulin and 61% to albumin)
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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.