berotralstat (Rx)

Brand and Other Names:Orladeyo

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 110mg
  • 150mg

Hereditary Angioedema

Indicated for prevention of hereditary angioedema (HAE) attacks

150 mg PO qDay

Dosage Modifications

Renal impairment

  • Mild-severe (CrCl >15 mL/min): No dosage adjustment necessary
  • End-stage renal disease (CrCl <15 mL/min or eGFR <15 mL/min/1.73 m2): Not recommended; not studied

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate or severe (Child-Pugh B or C): Reduce to 110 mg PO qDay

P-gp or BCRP inhibitors

  • Long-term administration of P-gp or BCRP inhibitors (eg, cyclosporine): Reduce berotralstat to 110 mg PO qDay

Persistent gastrointestinal (GI) reactions

  • Consider reducing to 110 mg PO qDay

Dosing Considerations

Limitations of use

  • Safety and efficacy not established for acute HAE attacks; do not use for treatment
  • Additional doses or doses >150 mg/day are not recommended owing to potential for QT prolongation

Dosage Forms & Strengths

capsule

  • 110mg
  • 150mg

Hereditary Angioedema

Indicated for prevention of hereditary angioedema (HAE) attacks in adults and adolescents aged 12 years and older

<12 years: Safety and efficacy not established

≥12 years

  • 150 mg PO qDay

Dosage Modifications

Renal impairment

  • Mild-severe (CrCl >15 mL/min): No dosage adjustment necessary
  • End-stage renal disease (CrCl <15 mL/min or eGFR <15 mL/min/1.73 m2): Not recommended; not studied

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate or severe (Child-Pugh B or C): Reduce to 110 mg PO qDay

P-gp or BCRP inhibitors

  • Long-term administration of P-gp or BCRP inhibitors (eg, cyclosporine): Reduce berotralstat to 110 mg PO qDay

Persistent gastrointestinal (GI) reactions

  • Reduce dose to 110 mg PO qDay

Dosing Considerations

Limitations of use

Safety and efficacy not established for acute HAE attacks; should not use for treatment

Additional doses or doses >150 mg/day are not recommended owing to potential for QT prolongation

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Interactions

Interaction Checker

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            Contraindicated (1)

            • lonafarnib

              berotralstat will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            Serious - Use Alternative (11)

            • carbamazepine

              carbamazepine decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • fosphenytoin

              fosphenytoin decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lorlatinib

              lorlatinib decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • primidone

              primidone decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • rifampin

              rifampin decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • tepotinib

              tepotinib will increase the level or effect of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • tipranavir

              tipranavir decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • vinblastine

              vinblastine decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            Monitor Closely (180)

            • abemaciclib

              berotralstat will increase the level or effect of abemaciclib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • acalabrutinib

              acalabrutinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • afatinib

              berotralstat will increase the level or effect of afatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • alfentanil

              berotralstat will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • aliskiren

              berotralstat will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ambrisentan

              berotralstat will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • amiodarone

              amiodarone increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of amiodarone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • apixaban

              berotralstat will increase the level or effect of apixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • artesunate

              berotralstat will increase the level or effect of artesunate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • atazanavir

              berotralstat will increase the level or effect of atazanavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • atorvastatin

              atorvastatin increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • avatrombopag

              berotralstat will increase the level or effect of avatrombopag by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • azithromycin

              azithromycin increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • bendamustine

              berotralstat will increase the level or effect of bendamustine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • betrixaban

              berotralstat will increase the level or effect of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • brentuximab vedotin

              berotralstat will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • budesonide

              berotralstat will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • capmatinib

              capmatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • carbamazepine

              berotralstat will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • carfilzomib

              berotralstat will increase the level or effect of carfilzomib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • carvedilol

              carvedilol increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ceritinib

              berotralstat will increase the level or effect of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • cetirizine

              berotralstat will increase the level or effect of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • cimetidine

              berotralstat will increase the level or effect of cimetidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ciprofloxacin

              berotralstat will increase the level or effect of ciprofloxacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • clarithromycin

              clarithromycin increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • cobicistat

              cobicistat increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • colchicine

              berotralstat will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • crizotinib

              berotralstat will increase the level or effect of crizotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • cyclosporine

              cyclosporine increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP and P-gp substrate) to 110 mg/day when coadministered with cyclosporine (a P-gp and BCRP inhibitor).

              berotralstat will increase the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              berotralstat will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • dabigatran

              berotralstat will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • dabrafenib

              dabrafenib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of dabrafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • daclatasvir

              daclatasvir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • darolutamide

              darolutamide increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • dasabuvir

              berotralstat will increase the level or effect of dasabuvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • daunorubicin

              berotralstat will increase the level or effect of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • daunorubicin liposomal

              berotralstat will increase the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • desloratadine

              berotralstat will increase the level or effect of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • desogestrel

              berotralstat increases levels of desogestrel by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration results in increased exposure to etonogestrel, the active metabolite of desogestrel; potential risk of concurrent use of desogestrel should be weighed against benefit.

            • dexamethasone

              berotralstat will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • digoxin

              berotralstat will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • dihydroergotamine

              berotralstat will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • diltiazem

              berotralstat will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • dipyridamole

              dipyridamole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • disopyramide

              berotralstat will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • docetaxel

              berotralstat will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • doxorubicin

              berotralstat will increase the level or effect of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • dronedarone

              dronedarone increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • duvelisib

              berotralstat will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • edoxaban

              berotralstat will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • elagolix

              elagolix increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • eletriptan

              berotralstat will increase the level or effect of eletriptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • elexacaftor

              elexacaftor increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • eliglustat

              eliglustat increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • eltrombopag

              eltrombopag increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • eluxadoline

              eluxadoline increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • erdafitinib

              erdafitinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • ergotamine

              berotralstat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • erythromycin base

              erythromycin base increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of erythromycin ethylsuccinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • erythromycin lactobionate

              erythromycin lactobionate increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of erythromycin lactobionate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • erythromycin stearate

              erythromycin stearate increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of erythromycin stearate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ethosuximide

              berotralstat will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • etoposide

              berotralstat will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • everolimus

              berotralstat will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              berotralstat will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • fentanyl

              berotralstat will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • fexofenadine

              berotralstat will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • flibanserin

              flibanserin increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • fostamatinib

              fostamatinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • fostemsavir

              fostemsavir increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • gefitinib

              gefitinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • grapefruit

              grapefruit increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • hydrocortisone

              berotralstat will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ibrutinib

              ibrutinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • idarubicin

              berotralstat will increase the level or effect of idarubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • imatinib

              imatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • indinavir

              berotralstat will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • irinotecan

              berotralstat will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • irinotecan liposomal

              berotralstat will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • istradefylline

              istradefylline increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • itraconazole

              itraconazole increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • ivermectin

              berotralstat will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ketoconazole

              ketoconazole increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              ketoconazole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • lapatinib

              lapatinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              lapatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • larotrectinib

              berotralstat will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lasmiditan

              lasmiditan increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              lasmiditan increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of ledipasvir/sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lefamulin

              berotralstat will increase the level or effect of lefamulin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lenvatinib

              berotralstat will increase the level or effect of lenvatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • letermovir

              berotralstat will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • levoketoconazole

              levoketoconazole increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              levoketoconazole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • linagliptin

              berotralstat will increase the level or effect of linagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lomitapide

              lomitapide increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • loperamide

              berotralstat will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lopinavir

              lopinavir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • loratadine

              berotralstat will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • lovastatin

              berotralstat will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • maraviroc

              berotralstat will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • mefloquine

              mefloquine increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • methotrexate

              berotralstat will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • midazolam

              berotralstat will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • mitomycin

              berotralstat will increase the level or effect of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • morphine

              berotralstat will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • nadolol

              berotralstat will increase the level or effect of nadolol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • naldemedine

              berotralstat will increase the level or effect of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • nelfinavir

              berotralstat will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • neratinib

              neratinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • nicardipine

              berotralstat will increase the level or effect of nicardipine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • nilotinib

              berotralstat will increase the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • nintedanib

              berotralstat will increase the level or effect of nintedanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ombitasvir/paritaprevir/ritonavir

              ombitasvir/paritaprevir/ritonavir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of ombitasvir/paritaprevir/ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ondansetron

              berotralstat will increase the level or effect of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • osimertinib

              osimertinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              osimertinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of osimertinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • paclitaxel

              berotralstat will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • paclitaxel protein bound

              berotralstat will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • paliperidone

              berotralstat will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • pantoprazole

              pantoprazole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • pazopanib

              berotralstat will increase the level or effect of pazopanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • pimozide

              berotralstat will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • pomalidomide

              berotralstat will increase the level or effect of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ponatinib

              ponatinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              ponatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • posaconazole

              posaconazole increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • pralsetinib

              berotralstat will increase the level or effect of pralsetinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • pravastatin

              berotralstat will increase the level or effect of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • prednisolone

              berotralstat will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • propafenone

              propafenone increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • quinidine

              quinidine increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of quinidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              berotralstat will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • quinine

              quinine increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of quinine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              berotralstat will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • ranolazine

              ranolazine increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • regorafenib

              regorafenib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • reserpine

              reserpine increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • rifampin

              berotralstat will increase the level or effect of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • rifaximin

              berotralstat will increase the level or effect of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • rimegepant

              berotralstat will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • riociguat

              berotralstat will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • risperidone

              berotralstat will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • ritonavir

              ritonavir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • rolapitant

              rolapitant increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              rolapitant increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • romidepsin

              berotralstat will increase the level or effect of romidepsin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • safinamide

              safinamide increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • saquinavir

              berotralstat will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • saxagliptin

              berotralstat will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • selumetinib

              selumetinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • silodosin

              berotralstat will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • simeprevir

              simeprevir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • sirolimus

              berotralstat will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • sitagliptin

              berotralstat will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • sofosbuvir

              berotralstat will increase the level or effect of sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • stiripentol

              stiripentol increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              stiripentol increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • sunitinib

              sunitinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • tacrolimus

              berotralstat will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              berotralstat will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • tafamidis

              tafamidis increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • tafamidis meglumine

              tafamidis meglumine increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • talazoparib

              berotralstat will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • tazemetostat

              berotralstat will increase the level or effect of tazemetostat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • temsirolimus

              berotralstat will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • teniposide

              berotralstat will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • tenofovir AF

              berotralstat will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • tenofovir DF

              berotralstat will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • testosterone

              berotralstat will increase the level or effect of testosterone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • tezacaftor

              tezacaftor increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • thioridazine

              berotralstat will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP2D6 substrates.

            • tolvaptan

              berotralstat will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • topotecan

              berotralstat will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • trabectedin

              berotralstat will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • triazolam

              berotralstat will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • tucatinib

              tucatinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • ubrogepant

              berotralstat will increase the level or effect of ubrogepant by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • vandetanib

              vandetanib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • velpatasvir

              velpatasvir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              velpatasvir increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of velpatasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • vemurafenib

              vemurafenib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              vemurafenib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • venetoclax

              berotralstat will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • verapamil

              berotralstat will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • vinblastine

              berotralstat will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • vincristine

              berotralstat will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • vincristine liposomal

              berotralstat will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • voclosporin

              berotralstat will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

            • voxilaprevir

              voxilaprevir increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

              berotralstat will increase the level or effect of voxilaprevir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            Minor (1)

            • verapamil

              verapamil increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

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            Adverse Effects

            >10%

            Abdominal pain (10-23%)

            Vomiting (10-15%)

            Diarrhea (10-15%)

            1-10%

            Gastroesophageal reflux disease (5-10%)

            Back pain (2-10%)

            Headache (9%)

            Fatigue (6%)

            Flatulence (6%)

            Frequency Not Defined

            In Trial 1, single patient discontinued treatment after a single 150-mg dose due to asymptomatic elevated ALT >8x ULN and AST >3x ULN and total bilirubin was normal

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            Warnings

            Contraindications

            None

            Cautions

            QT prolongation may occur at dosages >150 mg/day; additional doses or doses >150 mg/day are not recommended

            Drug interaction overview

            • Berotralstat is a P-gp and BCRP substrate, a P-gp inhibitor, a moderate CYP2D6 inhibitor, and weak CYP2D6 and CYP2C19 inhibitor
            • P-gp or BCRP inhibitors
              • Reduce berotralstat dose when coadministered
              • Cyclosporine, a P-gp and BCRP inhibitor, increased berotralstat peak plasma concentration by 25%, AUC(0-last) by 55%, and AUC(0-inf) by 69%
            • P-gp inducers
              • Avoid coadministration
              • P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration and efficacy
            • CYP2D6 or CYP3A4
              • Monitor or titrate substrate dose when coadministered with narrow therapeutic index drugs that are CYP2D6 or CYP3A substrates
              • Berotralstat moderately inhibits CYP2D6 or CYP3A4 at recommended dose (ie, 150 mg)
            • P-gp substrates
              • Monitoring or dose titration is recommended for P-gp substrates (eg, digoxin)
              • Berotralstat inhibits P-gp at higher than recommended dose (ie, 300 mg)
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            Pregnancy & Lactation

            Pregnancy

            Insufficient data available regarding use in pregnant females to inform drug-associated risks

            Animal data

            • No structural alterations observed when orally administered to pregnant rats and rabbits during organogenesis at doses up to ~10 and 2x, respectively, the maximum recommended human daily dose in adults based on AUC

            Lactation

            There are no data on drug presence in human milk, effects on breastfed infants, or effects on milk production

            Low levels of berotralstat detected in plasma of rat pups when oral administered to dams during lactation period; berotralstat concentration in pup plasma was ~2% of maternal plasma

            When drug is present in animal milk, it is likely the drug will be present in human milk

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Kallikrein inhibitor; binds to plasma kallikrein and inhibits its proteolytic activity

            Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE

            In patients with HAE caused by C1-inhibitor deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks

            Absorption

            Peak plasma time: 5 hr

            Peak plasma concentration at steady-state

            • 110 mg/day: 97.8 ng/mL
            • 150 mg/day: 158 ng/mL

            AUC at steady-state

            • 110 mg/day: 1,600 ng⋅hr/mL
            • 150 mg/day: 2,770 ng⋅hr/mL

            Steady-state

            • Reached at days 6-12
            • Exposure at steady state is ~5x that after a single dose

            Effect of food

            • No differences of peak plasma concentration and AUC with high-fat meal
            • Median peak plasma time was delayed by 3 hr

            Distribution

            Protein bound: ~99%

            Blood-to-plasma ratio: ~0.92

            Metabolism

            Metabolized by CYP2D6 and CYP3A4

            Elimination

            Half-life: ~93 hr

            Excretion: Urine (~9% [3.4% unchanged]); feces (79%)

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            Administration

            Oral Administration

            Administer with food

            Storage

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

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            Images

            No images available for this drug.
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            Patient Handout

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