selpercatinib (Rx)

Brand and Other Names:Retevmo
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 40mg
  • 80mg

Non-small Cell Lung Cancer

Indicated for metastatic RET fusion-positive non-small cell lung cancer (NSCLC)

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Medullary Thyroid Cancer

Indicated for advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in patients who required systemic therapy

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Thyroid Cancer

Indicated for advanced or metastatic RET fusion-positive thyroid cancer in patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations

  • Weight <50 kg
    • First reduction: 80 mg BID
    • Second reduction: 40 mg BID
    • Third reduction: 40 mg qDay
    • Permanently discontinue if unable to tolerate third dose reduction
  • Weight ≥50 kg
    • First reduction: 120 mg BID
    • Second reduction: 80 mg BID
    • Third reduction: 40 mg BID
    • Permanently discontinue if unable to tolerate third dose reduction

Hepatotoxicity grade 3 or 4

  • Withhold dosing and monitor AST/ALT once weekly until resolution to Grade 1 or baseline
  • Resume at reduced dose by 2 dose levels and monitor AST/ALT once weekly until 4 weeks after reaching dose taken prior to the onset of Grade 3 or 4 increased AST or ALT
  • Increase dose by 1 dose level after a minimum of 2 weeks without recurrence, and then increase to dose taken before Grade 3 or 4 increased AST or ALT after minimum of 4 weeks without recurrence

Hypertension

  • Grade 3: Withhold dosing for Grade 3 hypertension that persists despite optimal antihypertensive therapy; resume at reduced dose when hypertension controlled
  • Grade 4: Discontinue

QT prolongation

  • Grade 3: Withhold dosing until recovery to baseline or Grade ≤1; resume at reduced dose
  • Grade 4: Discontinue

Hemorrhagic events grade 3 or 4

  • Withhold dosing until recovery to baseline or Grade ≤1
  • Discontinue for severe or life-threatening hemorrhagic events

Hypersensitivity reactions all grades

  • Withhold dosing until resolution; initiate corticosteroids
  • Resume at reduced dose by 3 dose levels while continuing corticosteroids
  • Increase dose by 1 dose level each week until the dose taken prior to hypersensitivity event is reached, then taper corticosteroids

Other adverse effects grade 3 or 4

  • Withhold dosing until recovery to baseline or Grade ≤1
  • Resume at reduced dose

Coadministration with CYP3A inhibitors

  • Avoid coadministration; if unable to avoid, reduce selpercatinib dose
  • After inhibitor has been discontinued for 3-5 elimination half-lives, resume selpercatinib at dose take prior to initiated the CYP3A inhibitor
  • Moderate CYP3A inhibitor
    • If current dose is 120 mg BID, reduce to 80 mg BID
    • If current dose is 160 mg BID, reduce to 120 mg BID
  • Strong CYP3A inhibitor
    • If current dose is 120 mg BID, reduce to 40 mg BID
    • If current dose is 160 mg BID, reduce to 80 mg BID

Renal impairment

  • Mild-to-severe (CrCl ≥15 mL/min): No dose adjustment required
  • ESRD: Recommended dose not established

Hepatic impairment

  • Mild or moderate
    • No dose adjustment required
    • Mild defined as: TB ≤ULN with AST >ULN OR TB >1-1.5x ULN with any AST
    • Moderate defined as: TB >1.5-3x ULN with any AST
  • Severe
    • If current dose is 120 mg or 160 mg BID, reduce to 80 mg BID
    • Severe defined as: Total biliruvin (TB) >3-10x ULN with any AST

Acid-reducing agents

Avoid with PPIs, histamine-2 (H2) receptor antagonists, or locally acting antacids

  • If unable to avoid
    • PPIs: Take with food when coadministered
    • H2 receptor antagonist: Take selpercatinib 2 hr before or 10 hr after an H2 antagonist
    • Locally acting antacid: Take selpercatinib 2 hr before or 2 hr after antacid

Dosing Considerations

Select patients for treatment based on presence of RET gene fusion (NSCLC or thyroid cancer) or specific RET gene mutation (MTC) in tumor specimens or plasma

Dosage Forms & Strengths

capsule

  • 40mg
  • 80mg

Medullary Thyroid Cancer

Indicated for advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in children aged ≥12 years who required systemic therapy

<12 years: Safety and efficacy not established

≥12 years

  • <50 kg: 120 mg PO BID
  • ≥50 kg: 160 mg PO BID
  • Continue until disease progression or unacceptable toxicity

Thyroid Cancer

Indicated for advanced or metastatic RET fusion-positive thyroid cancer in children aged ≥12 years who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

<12 years: Safety and efficacy not established

≥12 years

  • <50 kg: 120 mg PO BID
  • ≥50 kg: 160 mg PO BID
  • Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations

  • Weight <50 kg
    • First reduction: 80 mg BID
    • Second reduction: 40 mg BID
    • Third reduction: 40 mg qDay
    • Permanently discontinue if unable to tolerate third dose reduction
  • Weight ≥50 kg
    • First reduction: 120 mg BID
    • Second reduction: 80 mg BID
    • Third reduction: 40 mg BID
    • Permanently discontinue if unable to tolerate third dose reduction

Hepatotoxicity grade 3 or 4

  • Withhold dosing and monitor AST/ALT once weekly until resolution to Grade 1 or baseline
  • Resume at reduced dose by 2 dose levels and monitor AST/ALT once weekly until 4 weeks after reaching dose taken prior to the onset of Grade 3 or 4 increased AST or ALT
  • Increase dose by 1 dose level after a minimum of 2 weeks without recurrence, and then increase to dose taken before Grade 3 or 4 increased AST or ALT after minimum of 4 weeks without recurrence

Hypertension

  • Grade 3: Withhold dosing for Grade 3 hypertension that persists despite optimal antihypertensive therapy; resume at reduced dose when hypertension controlled
  • Grade 4: Discontinue

QT prolongation

  • Grade 3: Withhold dosing until recovery to baseline or Grade ≤1; resume at reduced dose
  • Grade 4: Discontinue

Hemorrhagic events grade 3 or 4

  • Withhold dosing until recovery to baseline or Grade ≤1
  • Discontinue for severe or life-threatening hemorrhagic events

Hypersensitivity reactions all grades

  • Withhold dosing until resolution; initiate corticosteroids
  • Resume at reduced dose by 3 dose levels while continuing corticosteroids
  • Increase dose by 1 dose level each week until the dose taken prior to hypersensitivity event is reached, then taper corticosteroids

Other adverse effects grade 3 or 4

  • Withhold dosing until recovery to baseline or Grade ≤1
  • Resume at reduced dose

Coadministration with CYP3A inhibitors

  • Avoid coadministration; if unable to avoid, reduce selpercatinib dose
  • After inhibitor has been discontinued for 3-5 elimination half-lives, resume selpercatinib at dose take prior to initiated the CYP3A inhibitor
  • Moderate CYP3A inhibitor
    • If current dose is 120 mg BID, reduce to 80 mg BID
    • If current dose is 160 mg BID, reduce to 120 mg BID
  • Strong CYP3A inhibitor
    • If current dose is 120 mg BID, reduce to 40 mg BID
    • If current dose is 160 mg BID, reduce to 80 mg BID

Renal impairment

  • Mild-to-moderate (CrCl ≥30 mL/min): No dose adjustment required
  • Severe: (CrCl <30 mL/min) or ESRD: Recommended dose not established

Hepatic impairment

  • Mild or moderate
    • No dose adjustment required
    • Mild defined as: Total bilirubin (TB) ≤ULN with AST >ULN OR TB >1-1.5x ULN with any AST
    • Moderate defined as: TB >1.5-3x ULN with any AST
  • Severe
    • If current dose is 120 mg or 160 mg BID, reduce to 80 mg BID
    • Severe defined as: TB >3-10x ULN with any AST

Acid-reducing agents

Avoid with PPIs, histamine-2 (H2) receptor antagonists, or locally acting antacids

  • If unable to avoid
    • PPIs: Take with food when coadministered
    • H2 receptor antagonist: Take selpercatinib 2 hr before or 10 hr after an H2 antagonist
    • Locally acting antacid: Take selpercatinib 2 hr before or 2 hr after antacid

Dosing Considerations

Select patients for treatment based on presence of RET gene fusion (NSCLC or thyroid cancer) or specific RET gene mutation (MTC) in tumor specimens or plasma

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Interactions

Interaction Checker

and selpercatinib

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            Contraindicated (0)

              Serious - Use Alternative (44)

              • abametapir

                abametapir will increase the level or effect of selpercatinib 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.

              • amobarbital

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

              • apalutamide

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

              • aripiprazole

                aripiprazole and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • artemether

                artemether and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • artemether/lumefantrine

                artemether/lumefantrine and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • atazanavir

                atazanavir will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce selpercatinib dose from 120 mg BID to 40 mg BID, or from 160 mg BID to 80 mg BID. Following discontinuation of the strong CYP3A4 inhibitor, wait at least 3 to 5 half-lives of the discontinued drug before resuming the selpercatinib dose administered before use of the strong CYP3A4 inhibitor.

              • atomoxetine

                atomoxetine and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • bosentan

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

              • carbamazepine

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

              • ceritinib

                ceritinib and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • chloroquine

                chloroquine and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • clarithromycin

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

              • conivaptan

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

              • dabrafenib

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

              • darunavir

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

              • desflurane

                desflurane and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

              • efavirenz

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

              • enzalutamide

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

              • etravirine

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

              • fexinidazole

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

              • indinavir

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

              • itraconazole

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

              • ketoconazole

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

              • lonafarnib

                lonafarnib will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

                selpercatinib will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

              • lopinavir

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

              • lorlatinib

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

              • mitotane

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

              • nafcillin

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

              • nefazodone

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

              • nelfinavir

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

              • phenobarbital

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

              • phenytoin

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

              • ponesimod

                ponesimod, selpercatinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • posaconazole

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

              • primidone

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

              • ribociclib

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

              • rifabutin

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

              • rifampin

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

              • rifapentine

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

              • ritonavir

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

              • saquinavir

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

              • secobarbital

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

              Monitor Closely (120)

              • albuterol

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

              • alfuzosin

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

              • amiodarone

                selpercatinib increases toxicity of amiodarone by QTc interval. Use Caution/Monitor.

              • amitriptyline

                selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

              • amoxapine

                selpercatinib increases toxicity of amoxapine by QTc interval. Use Caution/Monitor.

              • apomorphine

                selpercatinib increases toxicity of apomorphine by QTc interval. Use Caution/Monitor.

              • arformoterol

                selpercatinib increases toxicity of arformoterol by QTc interval. Use Caution/Monitor.

              • arsenic trioxide

                selpercatinib increases toxicity of arsenic trioxide by QTc interval. Use Caution/Monitor.

              • artemether/lumefantrine

                selpercatinib increases toxicity of artemether/lumefantrine by QTc interval. Use Caution/Monitor.

              • asenapine

                selpercatinib increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

              • azithromycin

                selpercatinib increases toxicity of azithromycin by QTc interval. Use Caution/Monitor.

              • bedaquiline

                selpercatinib increases toxicity of bedaquiline by QTc interval. Use Caution/Monitor.

              • bosutinib

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

              • capecitabine

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

              • chloramphenicol

                chloramphenicol will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • chlorpromazine

                selpercatinib increases toxicity of chlorpromazine by QTc interval. Use Caution/Monitor.

              • ciprofloxacin

                selpercatinib increases toxicity of ciprofloxacin by QTc interval. Use Caution/Monitor.

              • cisapride

                selpercatinib increases toxicity of cisapride by QTc interval. Use Caution/Monitor.

              • citalopram

                selpercatinib increases toxicity of citalopram by QTc interval. Use Caution/Monitor.

              • clarithromycin

                selpercatinib increases toxicity of clarithromycin by QTc interval. Use Caution/Monitor.

              • clofazimine

                selpercatinib increases toxicity of clofazimine by QTc interval. Use Caution/Monitor.

              • clomipramine

                selpercatinib increases toxicity of clomipramine by QTc interval. Use Caution/Monitor.

              • clozapine

                selpercatinib increases toxicity of clozapine by QTc interval. Use Caution/Monitor.

              • cobicistat

                cobicistat will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, reduce dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily and to 80 mg PO twice daily if original dose was 160 mg twice daily; monitor for side effects

              • crizotinib

                selpercatinib increases toxicity of crizotinib by QTc interval. Use Caution/Monitor.

              • dasatinib

                selpercatinib increases toxicity of dasatinib by QTc interval. Use Caution/Monitor.

              • degarelix

                selpercatinib increases toxicity of degarelix by QTc interval. Use Caution/Monitor.

              • desipramine

                selpercatinib increases toxicity of desipramine by QTc interval. Use Caution/Monitor.

              • deutetrabenazine

                selpercatinib increases toxicity of deutetrabenazine by QTc interval. Use Caution/Monitor.

              • disopyramide

                selpercatinib increases toxicity of disopyramide by QTc interval. Use Caution/Monitor.

              • dofetilide

                selpercatinib increases toxicity of dofetilide by QTc interval. Use Caution/Monitor.

              • dolasetron

                selpercatinib increases toxicity of dolasetron by QTc interval. Use Caution/Monitor.

              • dronedarone

                selpercatinib increases toxicity of dronedarone by QTc interval. Use Caution/Monitor.

              • droperidol

                selpercatinib increases toxicity of droperidol by QTc interval. Use Caution/Monitor.

              • encorafenib

                selpercatinib increases toxicity of encorafenib by QTc interval. Use Caution/Monitor.

              • entrectinib

                selpercatinib increases toxicity of entrectinib by QTc interval. Use Caution/Monitor.

              • eribulin

                selpercatinib increases toxicity of eribulin by QTc interval. Use Caution/Monitor.

              • erythromycin base

                selpercatinib increases toxicity of erythromycin base by QTc interval. Use Caution/Monitor.

              • erythromycin ethylsuccinate

                selpercatinib increases toxicity of erythromycin ethylsuccinate by QTc interval. Use Caution/Monitor.

              • erythromycin lactobionate

                selpercatinib increases toxicity of erythromycin lactobionate by QTc interval. Use Caution/Monitor.

              • erythromycin stearate

                selpercatinib increases toxicity of erythromycin stearate by QTc interval. Use Caution/Monitor.

              • escitalopram

                selpercatinib increases toxicity of escitalopram by QTc interval. Use Caution/Monitor.

              • ezogabine

                selpercatinib increases toxicity of ezogabine by QTc interval. Use Caution/Monitor.

              • finerenone

                selpercatinib will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

              • flecainide

                selpercatinib increases toxicity of flecainide by QTc interval. Use Caution/Monitor.

              • fluconazole

                selpercatinib increases toxicity of fluconazole by QTc interval. Use Caution/Monitor.

              • fluoxetine

                selpercatinib increases toxicity of fluoxetine by QTc interval. Use Caution/Monitor.

              • fluphenazine

                selpercatinib increases toxicity of fluphenazine by QTc interval. Use Caution/Monitor.

              • formoterol

                selpercatinib increases toxicity of formoterol by QTc interval. Use Caution/Monitor.

              • foscarnet

                selpercatinib increases toxicity of foscarnet by QTc interval. Use Caution/Monitor.

              • gemifloxacin

                selpercatinib increases toxicity of gemifloxacin by QTc interval. Use Caution/Monitor.

              • gemtuzumab

                selpercatinib increases toxicity of gemtuzumab by QTc interval. Use Caution/Monitor.

              • glasdegib

                selpercatinib increases toxicity of glasdegib by QTc interval. Use Caution/Monitor.

              • haloperidol

                selpercatinib increases toxicity of haloperidol by QTc interval. Use Caution/Monitor.

              • hydroxychloroquine sulfate

                selpercatinib increases toxicity of hydroxychloroquine sulfate by QTc interval. Use Caution/Monitor.

              • ibutilide

                selpercatinib increases toxicity of ibutilide by QTc interval. Use Caution/Monitor.

              • idelalisib

                idelalisib will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, reduce the dose of selpercatinib to 40 mg PO BID if original dose was 120 mg BID, and to 80 mg PO BID if original dose was 160 mg BID

              • iloperidone

                selpercatinib increases toxicity of iloperidone by QTc interval. Use Caution/Monitor.

              • indacaterol, inhaled

                selpercatinib increases toxicity of indacaterol, inhaled by QTc interval. Use Caution/Monitor.

              • indapamide

                selpercatinib increases toxicity of indapamide by QTc interval. Use Caution/Monitor.

              • inotuzumab

                selpercatinib increases toxicity of inotuzumab by QTc interval. Use Caution/Monitor.

              • isradipine

                selpercatinib increases toxicity of isradipine by QTc interval. Use Caution/Monitor.

              • lapatinib

                selpercatinib increases toxicity of lapatinib by QTc interval. Use Caution/Monitor.

              • levofloxacin

                selpercatinib increases toxicity of levofloxacin by QTc interval. Use Caution/Monitor.

              • lofexidine

                selpercatinib increases toxicity of lofexidine by QTc interval. Use Caution/Monitor.

              • lopinavir

                selpercatinib increases toxicity of lopinavir by QTc interval. Use Caution/Monitor.

              • maprotiline

                selpercatinib increases toxicity of maprotiline by QTc interval. Use Caution/Monitor.

              • mefloquine

                selpercatinib increases toxicity of mefloquine by QTc interval. Use Caution/Monitor.

              • methadone

                selpercatinib increases toxicity of methadone by QTc interval. Use Caution/Monitor.

              • mifepristone

                selpercatinib increases toxicity of mifepristone by QTc interval. Use Caution/Monitor.

                mifepristone will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary and original dose selpercatinib was 120 mg twice daily, reduce dose to 40 mg PO twice daily; reduce dose to 80 mg PO twice daily if original dose was 160 mg twice daily; monitor ECGs for QT prolongation more frequently; if mifepristone is discontinued, resume original selpercatinib dose after 3 to 5 elimination half-lives of mifepristone

              • moxifloxacin

                selpercatinib increases toxicity of moxifloxacin by QTc interval. Use Caution/Monitor.

              • nilotinib

                selpercatinib increases toxicity of nilotinib by QTc interval. Use Caution/Monitor.

              • nortriptyline

                selpercatinib increases toxicity of nortriptyline by QTc interval. Use Caution/Monitor.

              • octreotide

                selpercatinib increases toxicity of octreotide by QTc interval. Use Caution/Monitor.

              • ofloxacin

                selpercatinib increases toxicity of ofloxacin by QTc interval. Use Caution/Monitor.

              • olanzapine

                selpercatinib increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.

              • ondansetron

                selpercatinib increases toxicity of ondansetron by QTc interval. Use Caution/Monitor.

              • osilodrostat

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

              • osimertinib

                selpercatinib increases toxicity of osimertinib by QTc interval. Use Caution/Monitor.

              • paliperidone

                selpercatinib increases toxicity of paliperidone by QTc interval. Use Caution/Monitor.

              • panobinostat

                selpercatinib increases toxicity of panobinostat by QTc interval. Use Caution/Monitor.

              • pasireotide

                selpercatinib increases toxicity of pasireotide by QTc interval. Use Caution/Monitor.

              • pazopanib

                selpercatinib increases toxicity of pazopanib by QTc interval. Use Caution/Monitor.

              • pentamidine

                selpercatinib increases toxicity of pentamidine by QTc interval. Use Caution/Monitor.

              • perphenazine

                selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

              • pimavanserin

                selpercatinib increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor.

              • pimozide

                selpercatinib increases toxicity of pimozide by QTc interval. Use Caution/Monitor.

              • pitolisant

                selpercatinib increases toxicity of pitolisant by QTc interval. Use Caution/Monitor.

              • posaconazole

                selpercatinib increases toxicity of posaconazole by QTc interval. Use Caution/Monitor.

              • procainamide

                selpercatinib increases toxicity of procainamide by QTc interval. Use Caution/Monitor.

              • propafenone

                selpercatinib increases toxicity of propafenone by QTc interval. Use Caution/Monitor.

              • protriptyline

                selpercatinib increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.

              • quetiapine

                selpercatinib increases toxicity of quetiapine by QTc interval. Use Caution/Monitor.

              • quinidine

                selpercatinib increases toxicity of quinidine by QTc interval. Use Caution/Monitor.

              • quinine

                selpercatinib increases toxicity of quinine by QTc interval. Use Caution/Monitor.

              • ranolazine

                selpercatinib increases toxicity of ranolazine by QTc interval. Use Caution/Monitor.

              • rilpivirine

                selpercatinib increases toxicity of rilpivirine by QTc interval. Use Caution/Monitor.

              • risperidone

                selpercatinib increases toxicity of risperidone by QTc interval. Use Caution/Monitor.

              • romidepsin

                selpercatinib increases toxicity of romidepsin by QTc interval. Use Caution/Monitor.

              • saquinavir

                selpercatinib increases toxicity of saquinavir by QTc interval. Use Caution/Monitor.

              • sertraline

                selpercatinib increases toxicity of sertraline by QTc interval. Use Caution/Monitor.

              • solifenacin

                selpercatinib increases toxicity of solifenacin by QTc interval. Use Caution/Monitor.

              • sorafenib

                selpercatinib increases toxicity of sorafenib by QTc interval. Use Caution/Monitor.

              • sotalol

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

              • sunitinib

                selpercatinib increases toxicity of sunitinib by QTc interval. Use Caution/Monitor.

              • tacrolimus

                selpercatinib increases toxicity of tacrolimus by QTc interval. Use Caution/Monitor.

              • telavancin

                selpercatinib increases toxicity of telavancin by QTc interval. Use Caution/Monitor.

              • tetrabenazine

                selpercatinib increases toxicity of tetrabenazine by QTc interval. Use Caution/Monitor.

              • thioridazine

                selpercatinib increases toxicity of thioridazine by QTc interval. Use Caution/Monitor.

              • thiothixene

                selpercatinib increases toxicity of thiothixene by QTc interval. Use Caution/Monitor.

              • toremifene

                selpercatinib increases toxicity of toremifene by QTc interval. Use Caution/Monitor.

              • trimipramine

                selpercatinib increases toxicity of trimipramine by QTc interval. Use Caution/Monitor.

              • vandetanib

                selpercatinib increases toxicity of vandetanib by QTc interval. Use Caution/Monitor.

              • vardenafil

                selpercatinib increases toxicity of vardenafil by QTc interval. Use Caution/Monitor.

              • vemurafenib

                selpercatinib increases toxicity of vemurafenib by QTc interval. Use Caution/Monitor.

              • vilanterol/fluticasone furoate inhaled

                selpercatinib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Use Caution/Monitor.

              • voclosporin

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

              • voriconazole

                selpercatinib increases toxicity of voriconazole by QTc interval. Use Caution/Monitor.

                voriconazole will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • vorinostat

                selpercatinib increases toxicity of vorinostat by QTc interval. Use Caution/Monitor.

              • ziprasidone

                selpercatinib increases toxicity of ziprasidone by QTc interval. Use Caution/Monitor.

              Minor (0)

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                Adverse Effects

                >10% All Grades

                Increased AST (51%)

                Increased ALT (45%)

                Increased glucose (44%)

                Decreased leukocytes (43%)

                Decreased albumin (42%)

                Decreased calcium (41%)

                Dry mouth (39%)

                Diarrhea (37%)

                Increased creatinine (37%)

                Increased alkaline phosphatase (36%)

                Hypertension (35%)

                Fatigue (35%)

                Edema (33%)

                Decreased platelets (33%)

                Increased total cholesterol (31%)

                Rash (27%)

                Decreased sodium (27%)

                Constipation (25%)

                Decreased magnesium (24%)

                Increased potassium (24%)

                Nausea (23%)

                Abdominal pain (23%)

                Headache (23%)

                Increased bilirubin (23%)

                Decreased glucose (22%)

                Cough (18%)

                Prolonged QT (17%)

                Dyspnea (16%)

                Vomiting (15%)

                Hemorrhage (15%)

                >10% Grades 3 and 4

                Hypertension (18%)

                1-10% Grades 3 and 4

                Increased ALT (9%)

                Increased AST (8%)

                Decreased sodium (7%)

                Prolonged QT (4%)

                Decreased calcium (3.8%)

                Diarrhea (3.4%)

                Decreased platelets (2.7%)

                Dyspnea (2.3%)

                Increased alkaline phosphatase (2.3%)

                Increased glucose (2.2%)

                Fatigue (2%)

                Increased bilirubin (2%)

                Abdominal pain (1.9%)

                Hemorrhage (1.9%)

                Decreased leukocytes (1.6%)

                Headache (1.4%)

                Increased potassium (1.2%)

                Increased creatinine (1%)

                <1% Grades 3 and 4

                Rash (0.7%)

                Decreased albumin (0.7%)

                Decreased glucose (0.7%)

                Constipation (0.6%)

                Nausea (0.6%)

                Decreased magnesium (0.6%)

                Vomiting (0.3%)

                Edema (0.3%)

                Increased total cholesterol (0.1%)

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                Warnings

                Contraindications

                None

                Cautions

                Also see Dosage Modifications for specific instructions on dose reductions for hepatotoxicity, hypertension, hemorrhagic events, hypersensitivity, and drug interactions

                Serious hepatic adverse reactions reported; monitor ALT and AST before initiating, q2Week during first 3 months, then monthly thereafter as clinically indicated; dose adjustment or discontinuation required based on severity

                Hypertension reported; manage with antihypertension medications; monitor blood pressure after 1 week and at least monthly thereafter as clinically indicated

                Monitor patients at significant risk of developing QTc prolongation; assess QT interval, electrolytes, and TSH at baseline and periodically during treatment

                Serious fatal hemorrhagic evens can occur; permanently discontinue with severe of life-threatening hemorrhage

                Hypersensitivity reported; signs and symptoms include fever, rash, and arthralgia or myalgia with concurrent decreased platelets or transaminitis; if hypersensitivity occurs, withhold drug and begin corticosteroids at dose of 1 mg/kg prednisone

                Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway; withhold for at least 7 days before elective surgery and do not administer for at least 2 weeks following major surgery and until adequate wound healing

                Tumor lysis syndrome (TLS) occurred in 1% of patients with medullary thyroid carcinoma receiving therapy; patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration; closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated

                Monitor growth plates in adolescent patients with open growth plates; consider interrupting or discontinuing therapy based on severity of any growth plate abnormalities and based on individual risk-benefit assessment

                Based on animal reproductive studies and its mechanism of action, can cause fetal harm

                Drug interaction overview

                • Strong or moderate CYP3A inhibitors or inducers
                  • Selpercatinib is predominantly metabolized by CYP3A4
                  • Avoid coadministration with strong or moderate CYP3A inhibitors or inducers
                  • Adjust selpercatinib dose if unable to avoid use with strong or moderate CYP3A4 inhibitors; see Dosage Modifications
                • Acid-reducing agents
                  • Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations, which may reduce efficacy
                  • Avoid concomitant use of PPIs, H2 receptor antagonists, and locally acting antacids
                  • If unable to avoid, take selpercatinib with food (with a PPI) or modify its administration time (with an H2 receptor antagonist or a locally acting antacid); see Administration
                • QT prolongation
                  • Selpercatinib associated with QTc interval prolongation
                  • Monitor QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong QT interval
                • CYP2C8 or CYP3A substrates
                  • Selpercatinib is a moderate CYP2C8 inhibitor and a weak CYP3A inhibitor
                  • Avoid coadministration with CYP2C8 or CYP3A substrates where minimal concentration changes may lead to increased adverse reactions
                  • If unable to avoid, follow any dose adjustment recommendations for CYP2C8 or CYP3A substrates provided in their product labeling
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                Pregnancy & Lactation

                Pregnancy

                Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant females

                Data are not available regarding use in pregnant females

                Verify pregnancy status in females of reproductive potential before initiating

                Advise patients of potential risk

                Animal studies

                • Administration to pregnant rats during organogenesis resulted in embryolethality and malformations at maternal exposures that were approximately equal to the human exposure at the clinical dose of 160 mg BID

                Contraception

                • Use effective contraception during treatment and for 1 week after final dose in females of reproductive potential and in males with female partners of reproductive potential

                Fertility

                • May impair fertility in females and males of reproductive potential

                Lactation

                Data are not available on the presence of selpercatinib or its metabolites in human milk or on their effects on breastfed children or milk production

                Advise women not to breastfeed during treatment and for 1 week after the final dose

                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

                Selpercatinib is a kinase inhibitor of wild-type rearranged during transfection (RET) and multiple mutated RET isoforms, as well as vascular endothelial growth factor receptors (VEGFR1, VEGFR3)

                Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth

                RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival; this dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET

                Absorption

                Absolute bioavailability: 73%

                Peak plasma time: 2 hr

                Peak plasma concentration: 2,980 ng/mL

                AUC: 51,600 ng⋅h/mL

                Steady-state reached: ~7 days

                Distribution

                Vd: 191 L

                Protein bound: 97%

                Metabolism

                Metabolized predominantly by CYP3A4

                Elimination

                Half-life: 32 hr

                Clearance: 6 L/hr

                Excretion: Feces (69% [14% unchanged]); urine (24% [12% unchanged])

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                Administration

                Oral Administration

                May take with or without food unless coadministered with a PPI

                Take with food if administered with a PPI

                Administer weight-based dose BID (~q12hr)

                Swallow capsule whole; do not crush or chew

                Missed dose: Do not take a missed dose unless it is more than 6 hr until next scheduled dose

                Vomited dose: Do not take an additional dose; resume dosing with the next scheduled dose

                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.
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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.