osilodrostat (Rx)

Brand and Other Names:Isturisa
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 1mg
  • 5mg
  • 10mg

Cushing Disease

Indicated for Cushing disease in adults for whom pituitary surgery is not an option or has not been curative

Initial: 2 mg PO BID

Titration

  • Initially, titrate by 1-2 mg BID, no more frequently than q2weeks based on rate of cortisol changes, individual tolerability, and improvement in Cushing disease signs and symptoms
  • If patient tolerates 10 mg PO BID and continues to have elevated 24-hr urine free cortisol (UFC) levels >ULN, titrate dosage further by 5 mg BID q2week
  • Monitor cortisol levels from at least two 24-hour UFC collections q1-2weeks until adequate clinical response maintained

Maintenance

  • Individualize maintenance dose according to cortisol levels and signs/symptoms
  • Maintenance dosage varied from 2-7 mg BID in clinical trials
  • Maximum recommended maintenance dose: 30 mg BID
  • Once maintenance dose achieved, monitor cortisol levels at least every 1-2 months or as indicated

Dosage Modifications

Interruptions or modifications

  • Decrease or temporarily discontinue if UFC levels fall below target range, there is a rapid decrease in cortisol levels, and/or symptoms of hypocortisolism occur; if necessary, initiate glucocorticoid
  • Stop osilodrostat and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency
  • If treatment is interrupted, reinitiate at lower dose when cortisol levels are within target ranges and symptoms have resolved

Renal impairment

  • No dose adjustment required
  • Caution in interpreting UFC levels with moderate-to-severe renal impairment, owing to reduced UFC excretion

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate (Child-Pugh B): Reduce initial dose to 1 mg BID
  • Severe (Child-Pugh C): Reduce initial dose to 1 mg qHS
  • May require more frequent adrenal function monitoring during dose titration in all patients with hepatic impairment

Dosing Considerations

Correct hypokalemia and hypomagnesemia before initiating

Obtain baseline ECG; repeat ECG within 1 week after treatment initiation, and as clinically indicated thereafter

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and osilodrostat

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (1)

            • lefamulin

              lefamulin will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            Serious - Use Alternative (10)

            • abametapir

              abametapir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • carbamazepine

              carbamazepine will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dofetilide

              dofetilide and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • fexinidazole

              fexinidazole and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of osilodrostat 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.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • grapefruit

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

            • mobocertinib

              mobocertinib and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • primidone

              primidone will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • tucatinib

              tucatinib will increase the level or effect of osilodrostat 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 (189)

            • albuterol

              osilodrostat and albuterol both increase QTc interval. Use Caution/Monitor.

              albuterol and osilodrostat both increase QTc interval. Use Caution/Monitor. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • alfuzosin

              osilodrostat and alfuzosin both increase QTc interval. Use Caution/Monitor.

              alfuzosin and osilodrostat both increase QTc interval. Use Caution/Monitor. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • amiodarone

              osilodrostat and amiodarone both increase QTc interval. Use Caution/Monitor.

            • amitriptyline

              osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • anagrelide

              osilodrostat and anagrelide both increase QTc interval. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • apomorphine

              osilodrostat and apomorphine both increase QTc interval. Use Caution/Monitor.

            • arformoterol

              osilodrostat and arformoterol both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              osilodrostat and aripiprazole both increase QTc interval. Use Caution/Monitor.

            • arsenic trioxide

              osilodrostat and arsenic trioxide both increase QTc interval. Use Caution/Monitor.

            • artemether

              osilodrostat and artemether both increase QTc interval. Use Caution/Monitor.

            • artemether/lumefantrine

              osilodrostat and artemether/lumefantrine both increase QTc interval. Use Caution/Monitor.

            • asenapine

              osilodrostat and asenapine both increase QTc interval. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • atomoxetine

              osilodrostat and atomoxetine both increase QTc interval. Use Caution/Monitor.

            • azithromycin

              osilodrostat and azithromycin both increase QTc interval. Use Caution/Monitor.

            • bedaquiline

              osilodrostat and bedaquiline both increase QTc interval. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • bosutinib

              osilodrostat and bosutinib both increase QTc interval. Use Caution/Monitor.

            • buprenorphine

              osilodrostat and buprenorphine both increase QTc interval. Use Caution/Monitor.

            • butabarbital

              butabarbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • butalbital

              butalbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • capecitabine

              osilodrostat and capecitabine both increase QTc interval. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • ceritinib

              osilodrostat and ceritinib both increase QTc interval. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • chloroquine

              osilodrostat and chloroquine both increase QTc interval. Use Caution/Monitor.

              chloroquine and osilodrostat both increase QTc interval. Use Caution/Monitor.

            • chlorpromazine

              osilodrostat and chlorpromazine both increase QTc interval. Use Caution/Monitor.

            • ciprofloxacin

              osilodrostat and ciprofloxacin both increase QTc interval. Use Caution/Monitor.

            • citalopram

              osilodrostat and citalopram both increase QTc interval. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and clarithromycin both increase QTc interval. Use Caution/Monitor.

            • clofazimine

              osilodrostat and clofazimine both increase QTc interval. Use Caution/Monitor.

            • clozapine

              osilodrostat and clozapine both increase QTc interval. Use Caution/Monitor.

            • cobicistat

              cobicistat will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • conivaptan

              conivaptan will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • crizotinib

              osilodrostat and crizotinib both increase QTc interval. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

              osilodrostat and dabrafenib both increase QTc interval. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • dasatinib

              osilodrostat and dasatinib both increase QTc interval. Use Caution/Monitor.

            • degarelix

              osilodrostat and degarelix both increase QTc interval. Use Caution/Monitor.

            • desflurane

              osilodrostat and desflurane both increase QTc interval. Use Caution/Monitor.

            • desipramine

              osilodrostat and desipramine both increase QTc interval. Use Caution/Monitor.

            • deutetrabenazine

              osilodrostat and deutetrabenazine both increase QTc interval. Use Caution/Monitor.

            • disopyramide

              osilodrostat and disopyramide both increase QTc interval. Use Caution/Monitor.

            • divalproex sodium

              osilodrostat will decrease the level or effect of divalproex sodium by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • dofetilide

              osilodrostat and dofetilide both increase QTc interval. Use Caution/Monitor.

            • dolasetron

              osilodrostat and dolasetron both increase QTc interval. Use Caution/Monitor.

            • donepezil

              osilodrostat and donepezil both increase QTc interval. Use Caution/Monitor.

            • doxepin

              osilodrostat and doxepin both increase QTc interval. Use Caution/Monitor.

            • dronedarone

              osilodrostat and dronedarone both increase QTc interval. Use Caution/Monitor.

            • droperidol

              osilodrostat and droperidol both increase QTc interval. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

              osilodrostat and efavirenz both increase QTc interval. Use Caution/Monitor.

            • eliglustat

              osilodrostat and eliglustat both increase QTc interval. Use Caution/Monitor.

            • encorafenib

              osilodrostat and encorafenib both increase QTc interval. Use Caution/Monitor.

            • entrectinib

              osilodrostat and entrectinib both increase QTc interval. Use Caution/Monitor.

            • enzalutamide

              enzalutamide will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • eribulin

              osilodrostat and eribulin both increase QTc interval. Use Caution/Monitor.

            • erythromycin base

              osilodrostat and erythromycin base both increase QTc interval. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              osilodrostat and erythromycin ethylsuccinate both increase QTc interval. Use Caution/Monitor.

            • erythromycin lactobionate

              osilodrostat and erythromycin lactobionate both increase QTc interval. Use Caution/Monitor.

            • erythromycin stearate

              osilodrostat and erythromycin stearate both increase QTc interval. Use Caution/Monitor.

            • escitalopram

              osilodrostat and escitalopram both increase QTc interval. Use Caution/Monitor.

              escitalopram and osilodrostat both increase QTc interval. Use Caution/Monitor. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • etravirine

              etravirine will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • ezogabine

              osilodrostat and ezogabine both increase QTc interval. Use Caution/Monitor.

            • fingolimod

              osilodrostat and fingolimod both increase QTc interval. Use Caution/Monitor.

            • flecainide

              osilodrostat and flecainide both increase QTc interval. Use Caution/Monitor.

            • floxuridine

              osilodrostat and floxuridine both increase QTc interval. Use Caution/Monitor.

            • fluconazole

              osilodrostat and fluconazole both increase QTc interval. Use Caution/Monitor.

            • fluoxetine

              osilodrostat and fluoxetine both increase QTc interval. Use Caution/Monitor.

            • fluphenazine

              osilodrostat and fluphenazine both increase QTc interval. Use Caution/Monitor.

            • formoterol

              osilodrostat and formoterol both increase QTc interval. Use Caution/Monitor.

            • foscarnet

              osilodrostat and foscarnet both increase QTc interval. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • fostemsavir

              osilodrostat and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gadoterate meglumine

              osilodrostat and gadoterate meglumine both increase QTc interval. Use Caution/Monitor.

            • gemifloxacin

              osilodrostat and gemifloxacin both increase QTc interval. Use Caution/Monitor.

            • gemtuzumab

              osilodrostat and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

              osilodrostat and gilteritinib both increase QTc interval. Use Caution/Monitor.

            • glasdegib

              osilodrostat and glasdegib both increase QTc interval. Use Caution/Monitor.

            • goserelin

              osilodrostat and goserelin both increase QTc interval. Use Caution/Monitor.

            • granisetron

              osilodrostat and granisetron both increase QTc interval. Use Caution/Monitor.

            • haloperidol

              osilodrostat and haloperidol both increase QTc interval. Use Caution/Monitor.

            • hydroxychloroquine sulfate

              osilodrostat and hydroxychloroquine sulfate both increase QTc interval. Use Caution/Monitor.

              hydroxychloroquine sulfate and osilodrostat both increase QTc interval. Use Caution/Monitor.

            • hydroxyzine

              osilodrostat and hydroxyzine both increase QTc interval. Use Caution/Monitor.

            • ibutilide

              osilodrostat and ibutilide both increase QTc interval. Use Caution/Monitor.

            • idelalisib

              idelalisib will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • iloperidone

              osilodrostat and iloperidone both increase QTc interval. Use Caution/Monitor.

            • indacaterol, inhaled

              osilodrostat and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • inotuzumab

              osilodrostat and inotuzumab both increase QTc interval. Use Caution/Monitor.

            • isoflurane

              osilodrostat and isoflurane both increase QTc interval. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • itraconazole

              itraconazole will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and itraconazole both increase QTc interval. Use Caution/Monitor.

            • ivosidenib

              ivosidenib will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

              osilodrostat and ivosidenib both increase QTc interval. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • lapatinib

              osilodrostat and lapatinib both increase QTc interval. Use Caution/Monitor.

            • lefamulin

              osilodrostat and lefamulin both increase QTc interval. Use Caution/Monitor.

            • lenvatinib

              osilodrostat and lenvatinib both increase QTc interval. Use Caution/Monitor.

            • leuprolide

              osilodrostat and leuprolide both increase QTc interval. Use Caution/Monitor.

            • levalbuterol

              osilodrostat and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levofloxacin

              osilodrostat and levofloxacin both increase QTc interval. Use Caution/Monitor.

            • lithium

              osilodrostat and lithium both increase QTc interval. Use Caution/Monitor.

            • lofexidine

              osilodrostat and lofexidine both increase QTc interval. Use Caution/Monitor.

            • loperamide

              osilodrostat and loperamide both increase QTc interval. Use Caution/Monitor.

            • lopinavir

              lopinavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and lopinavir both increase QTc interval. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • macimorelin

              osilodrostat and macimorelin both increase QTc interval. Use Caution/Monitor.

            • mefloquine

              osilodrostat and mefloquine both increase QTc interval. Use Caution/Monitor.

            • methadone

              osilodrostat and methadone both increase QTc interval. Use Caution/Monitor.

            • midostaurin

              osilodrostat and midostaurin both increase QTc interval. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and mifepristone both increase QTc interval. Use Caution/Monitor.

            • mirtazapine

              osilodrostat and mirtazapine both increase QTc interval. Use Caution/Monitor.

            • mitotane

              mitotane will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • moxifloxacin

              osilodrostat and moxifloxacin both increase QTc interval. Use Caution/Monitor.

            • nafcillin

              nafcillin will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • nefazodone

              nefazodone will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • nelfinavir

              nelfinavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • nevirapine

              nevirapine will decrease the level or effect of osilodrostat by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • nilotinib

              osilodrostat and nilotinib both increase QTc interval. Use Caution/Monitor.

            • nortriptyline

              osilodrostat and nortriptyline both increase QTc interval. Use Caution/Monitor.

            • ofloxacin

              osilodrostat and ofloxacin both increase QTc interval. Use Caution/Monitor.

            • olanzapine

              osilodrostat and olanzapine both increase QTc interval. Use Caution/Monitor.

            • olodaterol inhaled

              osilodrostat and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

            • ondansetron

              osilodrostat and ondansetron both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osilodrostat and osimertinib both increase QTc interval. Use Caution/Monitor.

            • oxaliplatin

              osilodrostat and oxaliplatin both increase QTc interval. Use Caution/Monitor.

            • ozanimod

              ozanimod and osilodrostat both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              osilodrostat and paliperidone both increase QTc interval. Use Caution/Monitor.

            • panobinostat

              osilodrostat and panobinostat both increase QTc interval. Use Caution/Monitor.

            • pasireotide

              osilodrostat and pasireotide both increase QTc interval. Use Caution/Monitor.

            • pazopanib

              osilodrostat and pazopanib both increase QTc interval. Use Caution/Monitor.

            • pentamidine

              osilodrostat and pentamidine both increase QTc interval. Use Caution/Monitor.

            • pentobarbital

              pentobarbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • phenobarbital

              phenobarbital will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • phenytoin

              phenytoin will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • pimavanserin

              osilodrostat and pimavanserin both increase QTc interval. Use Caution/Monitor.

            • pimozide

              osilodrostat and pimozide both increase QTc interval. Use Caution/Monitor.

            • pitolisant

              osilodrostat and pitolisant both increase QTc interval. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • primaquine

              osilodrostat and primaquine both increase QTc interval. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

            • procainamide

              osilodrostat and procainamide both increase QTc interval. Use Caution/Monitor.

            • propofol

              osilodrostat and propofol both increase QTc interval. Use Caution/Monitor.

            • quetiapine

              osilodrostat and quetiapine both increase QTc interval. Use Caution/Monitor.

            • quinidine

              osilodrostat and quinidine both increase QTc interval. Use Caution/Monitor.

            • quinine

              osilodrostat and quinine both increase QTc interval. Use Caution/Monitor.

            • ranolazine

              osilodrostat and ranolazine both increase QTc interval. Use Caution/Monitor.

            • ribociclib

              osilodrostat and ribociclib both increase QTc interval. Use Caution/Monitor.

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

            • rifabutin

              rifabutin will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • rifampin

              rifampin will decrease the level or effect of osilodrostat by Other (see comment). Use Caution/Monitor. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

              rifampin will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • rilpivirine

              osilodrostat and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • risperidone

              osilodrostat and risperidone both increase QTc interval. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • romidepsin

              osilodrostat and romidepsin both increase QTc interval. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • salmeterol

              osilodrostat and salmeterol both increase QTc interval. Use Caution/Monitor.

            • saquinavir

              saquinavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and saquinavir both increase QTc interval. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

            • selpercatinib

              selpercatinib and osilodrostat both increase QTc interval. Use Caution/Monitor.

            • sertraline

              osilodrostat and sertraline both increase QTc interval. Use Caution/Monitor.

            • siponimod

              osilodrostat and siponimod both increase QTc interval. Use Caution/Monitor.

            • solifenacin

              osilodrostat and solifenacin both increase QTc interval. Use Caution/Monitor.

            • sorafenib

              osilodrostat and sorafenib both increase QTc interval. Use Caution/Monitor.

            • sotalol

              osilodrostat and sotalol both increase QTc interval. Use Caution/Monitor.

            • stiripentol

              stiripentol, osilodrostat. Other (see comment). Modify Therapy/Monitor Closely. Comment: Stiripentol is both an inhibitor and inducer of CYP2B6, and CYP3A4. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with stiripentol. Adjust dose of osilodrostat if necessary.

            • sunitinib

              osilodrostat and sunitinib both increase QTc interval. Use Caution/Monitor.

            • tacrolimus

              osilodrostat and tacrolimus both increase QTc interval. Use Caution/Monitor.

            • telavancin

              osilodrostat and telavancin both increase QTc interval. Use Caution/Monitor.

            • terbutaline

              osilodrostat and terbutaline both increase QTc interval. Use Caution/Monitor.

            • tetrabenazine

              osilodrostat and tetrabenazine both increase QTc interval. Use Caution/Monitor.

            • theophylline

              osilodrostat will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • thioridazine

              osilodrostat and thioridazine both increase QTc interval. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

            • tizanidine

              osilodrostat will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • toremifene

              osilodrostat and toremifene both increase QTc interval. Use Caution/Monitor.

            • trazodone

              osilodrostat and trazodone both increase QTc interval. Use Caution/Monitor.

            • triclabendazole

              osilodrostat and triclabendazole both increase QTc interval. Use Caution/Monitor.

            • triptorelin

              osilodrostat and triptorelin both increase QTc interval. Use Caution/Monitor.

            • valproic acid

              osilodrostat will decrease the level or effect of valproic acid by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • vandetanib

              osilodrostat and vandetanib both increase QTc interval. Use Caution/Monitor.

            • vardenafil

              osilodrostat and vardenafil both increase QTc interval. Use Caution/Monitor.

            • vemurafenib

              osilodrostat and vemurafenib both increase QTc interval. Use Caution/Monitor.

            • voclosporin

              voclosporin, osilodrostat. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and voriconazole both increase QTc interval. Use Caution/Monitor.

            • vorinostat

              osilodrostat and vorinostat both increase QTc interval. Use Caution/Monitor.

            • ziprasidone

              osilodrostat and ziprasidone both increase QTc interval. Use Caution/Monitor.

            Minor (0)

              Previous
              Next:

              Adverse Effects

              >10%

              Adrenal insufficiency (43.1%)

              Fatigue (38.7%)

              Nausea (37.2%)

              Headache (30.7%)

              Edema (21.2%)

              Nasopharyngitis (19.7%)

              Vomiting (19%)

              Arthralgia (17.5%)

              Back pain (15.3%)

              Rash (15.3%)

              Diarrhea (14.6%)

              Blood corticotrophin increased (13.9%)

              Dizziness (13.9%)

              Abdominal pain (13.1%)

              Hypokalemia (12.4%)

              Myalgia (12.4%)

              Decreased appetite (11.7%)

              Hormone level abnormal (11.7%)

              Hypotension (11.7%)

              Urinary tract infection (11.7%)

              Blood testosterone increased (10.9%)

              Pyrexia (10.9%)

              Anemia (10.2%)

              Cough (10.2%)

              Hypertension (10.2%)

              Influenza (10.2%)

              1-10%

              Hirsutism (9.5%)

              Acne (8.8%)

              Dyspepsia (8%)

              Insomnia (8%)

              Anxiety (7.3%)

              Depression (7.3%)

              Gastroenteritis (7.3%)

              Malaise (6.6%)

              Tachycardia (6.6%)

              Alopecia (5.8%)

              Transaminases increased (4.4%)

              ECG QT prolongation (3.6%)

              Syncope (1.5%)

              Previous
              Next:

              Warnings

              Contraindications

              None

              Cautions

              Hypocortisolism

              • Osilodrostat lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency
              • Lowering of cortisol can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, dizziness; significant lowering may result in hypotension, abnormal electrolyte levels, and hypoglycemia
              • Can occur at any time during treatment; evaluate for precipitating causes of hypocortisolism (eg, infection, physical stress)
              • Monitor 24-hr urine free cortisol (UFC), serum or plasma cortisol, and signs/symptoms
              • Decrease or temporarily discontinue osilodrostat if UFC levels fall below target range, there is a rapid decrease in cortisol levels, and/or symptoms of hypocortisolism occur
              • Stop osilodrostat and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency
              • Reinitiate at lower dose when urine free, serum, or plasma cortisol levels are within target range, and/or patient symptoms have resolved
              • After discontinuation, cortisol suppression may persist beyond the 4 hr drug half-life

              QTc prolongation

              • Associated with dose-dependent QT interval prolongation (maximum mean estimated QTcF increase of up to 5.3 ms at 30 mg), which may cause cardiac arrhythmias
              • Obtain baseline ECG with QTc interval measurement before initiating and monitor QTc interval thereafter
              • Correct hypokalemia and/or hypomagnesemia before initiating and monitor periodically during treatment; correct electrolyte abnormalities if indicated
              • Consider temporary discontinuation if QTc interval >480 ms
              • Caution with risk factors for QT prolongation, (eg, congenital long QT syndrome, CHF, bradyarrhythmias, uncorrected electrolyte abnormalities, other drugs known to prolong QT) and consider more frequent ECG monitoring

              Elevated adrenal hormone precursors and androgens

              • Osilodrostat blocks cortisol synthesis and may increase circulating levels of cortisol and aldosterone precursors (11-deoxy cortisol and 11-deoxycorticosterone) and androgens
              • Elevated 11-deoxycorticosterone levels may activate mineralocorticoid receptors and cause hypokalemia, edema, and hypertension
              • Correct hypokalemia before initiating
              • Monitor for hypokalemia, worsening hypertension, and edema
              • Treat osilodrostat-induced hypokalemia with IV or oral potassium supplementation based on event severity; if hypokalemia persists despite potassium supplementation, consider adding mineralocorticoid antagonists; osilodrostat dose reduction or discontinuation may be necessary
              • Accumulation of androgens may lead to hirsutism, hypertrichosis, and acne (in females)

              Drug interaction overview

              • Strong CYP3A4 inhibitors
                • Osilodrostat is a substrate of CYP3A4 substrate (major)
                • Reduce osilodrostat dose by 50% if coadministered with strong CYP3A4 inhibitors
              • Strong CYP3A4 and/or CYP2B6 inducers
                • Osilodrostat is a substrate of CYP3A4 (major) and CYP2B6 (moderate)
                • Coadministration with strong CYP3A4 and/or CYP2B6 inducers may decrease osilodrostat concentration and reduce efficacy
                • Discontinuation of strong CYP3A4 and/or CYP2B6 inducers while using osilodrostat may increase osilodrostat concentration and the related adverse effects
              • CYP1A2 and CYP2C19 substrates
                • Osilodrostat showed inhibition potential on CYP1A2 and CYP2C19 in clinical studies
                • Caution if coadministered with CYP1A2 or CYP2C19 substrates with a narrow therapeutic index
              • QTc prolonging drugs
                • Osilodrostat is associated with dose-dependent QT interval prolongation
                • Caution if coadministered with other drugs known to prolong QT interval
              Previous
              Next:

              Pregnancy & Lactation

              Pregnancy

              Data are not available regarding use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

              There are risks to the mother and fetus associated with active Cushing syndrome during pregnancy

              Clinical considerations

              • Active Cushing syndrome during pregnancy associated with increased risk of maternal and fetal morbidity and mortality (including gestational diabetes, gestational hypertension, preeclampsia, maternal death, miscarriage, fetal loss, preterm birth)

              Animal data

              • No adverse developmental outcomes observed in reproduction studies in pregnant rats and rabbits when exposed during organogenesis at doses that produced maternal exposures of 7 and 0.5 times the 30-mg BID maximum clinical dose, by AUC
              • In rabbits, exposures associated with maternal toxicity at 7 times the maximum clinical dose resulted in decreased fetal viability
              • No adverse developmental outcomes were observed in a prenatal and postnatal development study with administration to pregnant rats from organogenesis through lactation at 8 times the 30-mg BID maximum clinical dose

              Lactation

              Data are not available regarding presence in human or animal milk, effects on breastfed infants, or effects on milk production

              Because of potential for serious adverse effects (eg, adrenal insufficiency), do not breastfeed during treatment and for at least 1 week after discontinuing drug

              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.

              Previous
              Next:

              Pharmacology

              Mechanism of Action

              Orally administered steroidogenesis inhibitor of 11-beta-hydroxylase, an enzyme that catalyzes the final step of cortisol synthesis in the adrenal cortex

              Absorption

              Peak plasma time: 1 hr

              Distribution

              Protein bound: 36.4%

              Vd: 100 L

              Metabolism

              Multiple CYP enzymes (ie, CYP3A4, CYP2B6, CYP2D6) and UDP-glucuronosyltransferases contribute to metabolism

              No single enzyme contributes >25% to total clearance

              Metabolites are not expected to contribute to the pharmacological effect

              Elimination

              Half-life: 4 hr

              Excretion: 90.6% urine (5.2% as unchanged); 1.58% feces

              Previous
              Next:

              Administration

              Oral Administration

              May take with or without food

              Missed dose: Take next dose at the regularly scheduled time

              Storage

              Store at room temperature of 68-77ºF (20-25ºC); excursions permitted to 15-30ºC (59-86ºF)

              Protect from moisture

              Previous
              Next:

              Images

              No images available for this drug.
              Previous
              Next:

              Patient Handout

              A Patient Handout is not currently available for this monograph.
              Previous
              Next:

              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              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.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
              Additional Offers
              Email to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Email Forms to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Previous
              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.