Dosing & Uses
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
Other RET Fusion-Positive Solid Tumors
Indicated for locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options
<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
Interstitial lung disease/ pneumonitis
- Grade 2: Withhold until resolution; resume at a reduced dose; discontinue for recurrent ILD/pneumonitis
- Grade 3 or 4: Discontinue for confirmed ILD/pneumonitis
Hypothyroidism
- Grade 3 or 4: Withhold until resolution to Grade 1 or baseline; discontinue based on severity
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
Interstitial lung disease/ pneumonitis
- Grade 2: Withhold until resolution; resume at a reduced dose; discontinue for recurrent ILD/pneumonitis
- Grade 3 or 4: Discontinue for confirmed ILD/pneumonitis
Hypothyroidism
- Grade 3 or 4: Withhold until resolution to Grade 1 or baseline; discontinue based on severity
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (66)
- adagrasib
adagrasib, selpercatinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
- amisulpride
amisulpride and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
- amobarbital
amobarbital will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- anagrelide
anagrelide and selpercatinib both increase QTc interval. 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.
- buprenorphine
buprenorphine and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine buccal
buprenorphine buccal and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine subdermal implant
buprenorphine subdermal implant and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine transdermal
buprenorphine transdermal and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and selpercatinib both increase QTc interval. 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.
ceritinib will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- donepezil
donepezil 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.
efavirenz and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug. - eliglustat
eliglustat and selpercatinib both increase QTc interval. 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.
- fingolimod
fingolimod and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- fosphenytoin
fosphenytoin will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- gadobenate
gadobenate and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- gilteritinib
gilteritinib and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- granisetron
granisetron and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- hydroxyzine
hydroxyzine and selpercatinib both increase QTc interval. 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.
- isoflurane
isoflurane and selpercatinib both increase QTc interval. 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.
itraconazole and selpercatinib both increase QTc interval. 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.
- levoketoconazole
levoketoconazole will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lithium
lithium and selpercatinib both increase QTc interval. 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.
- mirtazapine
mirtazapine and selpercatinib both increase QTc interval. 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.
- oxaliplatin
oxaliplatin and selpercatinib both increase QTc interval. 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.
- primaquine
primaquine and selpercatinib both increase QTc interval. 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.
- sevoflurane
sevoflurane and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- siponimod
siponimod and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
Monitor Closely (129)
- 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.
- asenapine transdermal
asenapine transdermal and selpercatinib both increase QTc interval. Use Caution/Monitor.
- atogepant
selpercatinib will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- daprodustat
selpercatinib will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment
- 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. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
- 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.
- doxepin
doxepin and selpercatinib both increase 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.
- floxuridine
floxuridine and selpercatinib both increase 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.
- isavuconazonium sulfate
selpercatinib will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- lenacapavir
lenacapavir will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of moderate CYP3A4 inhibitors with selpercatinib. If unavoidable, reduce selpercatinib dose from 120 mg BID to 80 mg twice daily, or from 160 mg BID to 120 mg BID. After discontinuing the moderate CYP3A4 inhibitor, allow a period of at least 3-5 half-lives of the discontinued drug to elapse before resuming selpercatinib at dose before use of CYP3A4 inhibitor.
- 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.
- quizartinib
quizartinib, selpercatinib. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.
- 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.
- valbenazine
valbenazine and selpercatinib both increase 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 (4)
- acetazolamide
acetazolamide will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
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%)
Postmarketing Reports
Interstitial lung disease/pneumonitis
Hypothyroidism
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
Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur; monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold and promptly investigate for ILD in any patient who presents with acute or worsening respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough, and fever); withhold, reduce dose or permanently discontinue therapy based on severity of confirmed ILD
May cause hypothyroidism; monitor thyroid function before treatment and periodically during treatment; treat with thyroid hormone replacement as clinically indicated; withhold therapy until clinically stable or permanently discontinue based on severity
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
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.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])
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)
Images
Formulary
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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.
