pralsetinib (Rx)

Brand and Other Names:Gavreto
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg

Non-Small Cell Lung Cancer

Indicated for metastatic rearranged during transfection (RET) gene-positive non-small cell lung cancer (NSCLC)

400 mg PO qDay on an empty stomach

Continue until disease progression or until unacceptable toxicity

Medullary Thyroid Cancer

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

400 mg PO qDay

Continue until disease progression or until unacceptable toxicity

Thyroid Cancer

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

400 mg PO qDay

Continue until disease progression or until unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

  • First dose reduction: 300 mg PO qDay
  • Second dose reduction: 200 mg PO qDay
  • Third dose reduction: 100 mg PO qDay
  • Unable to tolerate 100 mg qDay: Permanently discontinue

Interstitial lung disease (ILD)/pneumonitis

  • Grade 1 or 2: Withhold until resolution; resume at reduced dose
  • Grade 3 or 4 or recurrent ILD/pneumonitis: Permanent discontinue

Hypertension

  • Grade 3: Withhold for persistent Grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose once hypertension controlled
  • Grade 4: Discontinue

Hepatoxicity

  • Grade 3 or 4: Withhold and monitor AST/ALT once weekly until resolution to Grade ≤1
  • Resume at reduced dose
  • If Grade ≥3 hepatotoxicity recurs, discontinue

Hemorrhagic events

  • Grade 3 or 4: Withhold until recovery to baseline or Grade ≤1
  • Discontinue for severe or life-threatening hemorrhagic events

Other adverse reactions

  • Grade 3 or 4: Withhold until recovery to Grade ≤2; resume at reduced dose
  • Recurrent Grade 4: Permanently discontinue

Strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors

  • Avoid coadministration
  • Dosage modification if unable to avoid combined P-gp and strong CYP3A4 inhibitors
    • If current pralsetinib dose is 300 or 400 mg qDay, reduce to 200 mg qDay
    • If current pralsetinib dose is 200 mg qDay, reduce to 100 mg qDay
    • After inhibitor has been discontinued for 3-5 elimination half-lives, resume at dose taken before initiating combined P-gp and strong CYP3A inhibitor

Strong CYP3A4 inducers

  • Avoid coadministration
  • If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer
  • After inducer has been discontinued for at least 14 days, resume pralsetinib at dose taken before initiating strong CYP3A inducer

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <15 mL/min): Not studied

Hepatic impairment

  • Mild (total bilirubin ≤ULN and AST >ULN OR total bilirubin >1-1.5x ULN and any AST): No dosage adjustment necessary
  • Moderate-to-severe (total bilirubin >1.5x ULN and any AST): Not studied

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiation

Patient selection

Medullary Thyroid Cancer

Indicated for advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in adults and adolescents aged ≥12 years who require systemic therapy

<12 years: Safety and efficacy not established

≥12 years

  • 400 mg PO qDay
  • Continue until disease progression or until unacceptable toxicity

Thyroid Cancer

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

<12 years: Safety and efficacy not established

≥12 years

  • 400 mg PO qDay
  • Continue until disease progression or until unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

  • First dose reduction: 300 mg PO qDay
  • Second dose reduction: 200 mg PO qDay
  • Third dose reduction: 100 mg PO qDay
  • Unable to tolerate 100 mg qDay: Permanently discontinue

Interstitial lung disease (ILD)/pneumonitis

  • Grade 1 or 2: Withhold until resolution; resume at reduced dose
  • Grade 3 or 4 or recurrent ILD/pneumonitis: Permanently discontinue

Hypertension

  • Grade 3: Withhold for persistent Grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose once hypertension controlled
  • Grade 4: Discontinue

Hepatoxicity

  • Grade 3 or 4: Withhold and monitor AST/ALT once weekly until resolution to Grade ≤1
  • Resume at reduced dose
  • If Grade ≥3 hepatotoxicity recurs, discontinue

Hemorrhagic events

  • Grade 3 or 4: Withhold until recovery to baseline or Grade ≤1
  • Discontinue for severe or life-threatening hemorrhagic events

Other adverse reactions

  • Grade 3 or 4: Withhold until recovery to Grade ≤2; resume at reduced dose
  • Recurrent Grade 4: Permanently discontinue

Strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors

  • Avoid coadministration
  • Dosage modification if unable to avoid combined P-gp and strong CYP3A4 inhibitors
    • If current pralsetinib dose is 300 or 400 mg qDay, reduce to 200 mg qDay
    • If current pralsetinib dose is 200 mg qDay, reduce to 100 mg qDay
    • After inhibitor has been discontinued for 3-5 elimination half-lives, resume at dose taken before initiating combined P-gp and strong CYP3A inhibitor

Strong CYP3A4 inducers

  • Avoid coadministration
  • If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer
  • After inducer has been discontinued for at least 14 days, resume pralsetinib at dose taken before initiating strong CYP3A inducer

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <15 mL/min): Not studied

Hepatic impairment

  • Mild (total bilirubin ≤ULN and AST >ULN OR total bilirubin >1-1.5x ULN and any AST): No dosage adjustment necessary
  • Moderate-to-severe (total bilirubin >1.5x ULN and any AST): Not studied

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiation

Patient selection

Next:

Interactions

Interaction Checker

and pralsetinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (51)

              • amobarbital

                amobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • apalutamide

                apalutamide will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • atazanavir

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

              • bosentan

                bosentan will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • butabarbital

                butabarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • butalbital

                butalbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • carbamazepine

                carbamazepine will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • chloramphenicol

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

              • clarithromycin

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

              • cobicistat

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

              • conivaptan

                conivaptan will increase the level or effect of pralsetinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.

              • dabrafenib

                dabrafenib will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • darunavir

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

              • efavirenz

                efavirenz will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • enzalutamide

                enzalutamide will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • etravirine

                etravirine will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • grapefruit

                grapefruit will increase the level or effect of pralsetinib by Other (see comment). Avoid or Use Alternate Drug. Combined CYP3A4 and P-gp inhibitors increase levels of pralsetinib, a CYP3A4 and P-gp substrate. If unable to avoid, reduce dose (see pralsetinib prescribing information). After combined P-gp and strong CYP3A4 inhibitor discontinued, resume previous pralsetinib dose.

              • idelalisib

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

              • indinavir

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

              • isoniazid

                isoniazid will increase the level or effect of pralsetinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.

              • itraconazole

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

              • ivosidenib

                ivosidenib will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • ketoconazole

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

              • lopinavir

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

              • lorlatinib

                lorlatinib will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • mifepristone

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

              • mitotane

                mitotane will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • nafcillin

                nafcillin will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • nefazodone

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

              • nelfinavir

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

              • pentobarbital

                pentobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • phenobarbital

                phenobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • phenytoin

                phenytoin will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • posaconazole

                posaconazole will increase the level or effect of pralsetinib by Other (see comment). Avoid or Use Alternate Drug. Combined CYP3A4 and P-gp inhibitors increase levels of pralsetinib, a CYP3A4 and P-gp substrate. If unable to avoid, reduce dose (see pralsetinib prescribing information). After combined P-gp and strong CYP3A4 inhibitor discontinued, resume previous pralsetinib dose.

              • primidone

                primidone will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • rifabutin

                rifabutin will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • rifampin

                rifampin will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • rifapentine

                rifapentine will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • ritonavir

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

              • rucaparib

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

              • saquinavir

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

              • secobarbital

                secobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • sotorasib

                sotorasib will decrease the level or effect of pralsetinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • St John's Wort

                St John's Wort will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

              • stiripentol

                stiripentol increases toxicity of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • tepotinib

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

              • tipranavir

                tipranavir will increase the level or effect of pralsetinib by Other (see comment). Avoid or Use Alternate Drug. Combined CYP3A4 and P-gp inhibitors increase levels of pralsetinib, a CYP3A4 and P-gp substrate. If unable to avoid, reduce dose (see pralsetinib prescribing information). After combined P-gp and strong CYP3A4 inhibitor discontinued, resume previous pralsetinib dose.

              • voriconazole

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

              Monitor Closely (2)

              • berotralstat

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

              • lonafarnib

                lonafarnib will increase the level or effect of pralsetinib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                >10%

                All grades

                • NSCLC
                  • Increased AST (69%)
                  • Increased ALT (46%)
                  • Decreased hemoglobin (54%)
                  • Decreased lymphocytes (52%)
                  • Decreased neutrophils (52%)
                  • Increased creatinine (42%)
                  • Increased alkaline phosphatase (40%)
                  • Constipation (35%)
                  • Fatigue (35%)
                  • Musculoskeletal pain (32%)
                  • Decreased calcium (corrected) (29%)
                  • Hypertension (28%)
                  • Decreased sodium (27%)
                  • Decreased phosphate (27%)
                  • Decreased platelets (26%)
                  • Diarrhea (24%)
                  • Cough (23%)
                  • Pyrexia (20%)
                  • Edema (20%)
                  • Pneumonia (17%)
                  • Dry mouth (16%)
                • Thyroid cancer
                  • Decreased calcium (corrected) (70%)
                  • Increased AST (69%)
                  • Decreased lymphocytes (67%)
                  • Decreased hemoglobin (63%)
                  • Decreased neutrophils (59%)
                  • Increased ALT (43%)
                  • Musculoskeletal pain (42%)
                  • Constipation (41%)
                  • Increased creatinine (41%)
                  • Decreased albumin (41%)
                  • Hypertension (40%)
                  • Increased phosphate (40%)
                  • Fatigue (38%)
                  • Diarrhea (34%)
                  • Decreased platelets (31%)
                  • Edema (29%)
                  • Decreased sodium (28%)
                  • Decreased phosphate (28%)
                  • Cough (27%)
                  • Decreased magnesium (27%)
                  • Decreased magnesium (27%)
                  • Increased potassium (26%)
                  • Headache (24%)
                  • Rash (24%)
                  • Increased bilirubin (24%)
                  • Increased alkaline phosphatase (22%)
                  • Dyspnea (22%)
                  • Pyrexia (22%)
                  • Peripheral neuropathy (20%)
                  • Dizziness (19%)
                  • Dysgeusia (17%)
                  • Abdominal pain (17%)
                  • Dry mouth (17%)
                  • Stomatitis (17%)
                  • Nausea (17%)
                  • Decreased appetite (15%)
                  • Tumor lysis syndrome (≤15%)
                  • Increased creatinine phosphokinase (≤15%)

                Grade 3-4

                • NSCLC
                  • Decreased lymphocytes (20%)
                  • Hypertension (14%)
                • Thyroid cancer
                  • Decreased lymphocytes (27%)
                  • Hypertension (21%)
                  • Decreased neutrophils (16%)
                  • Decreased hemoglobin (13%)

                1-10%

                All grades

                • NSCLC
                  • Hyperphosphatemia (10%)
                  • Pneumonitis (10%)

                Grade 3-4

                • NSCLC
                  • Decreased neutrophils (10%)
                  • Decreased phosphate (9%)
                  • Pneumonia (8%)
                  • Decreased hemoglobin (5%)
                  • Decreased sodium (3.2%)
                  • Diarrhea (3.2%)
                  • Pneumonitis (2.7%)
                  • Fatigue (2.3%)
                  • Decreased calcium (corrected) (2.2%)
                  • Increased ALT (2.1%)
                  • Sepsis (≥2%)
                  • Increased AST (1.1%)
                  • Increased creatinine (1.1%)
                  • Increased alkaline phosphatase (1.1%)
                  • Constipation (1%)
                • Thyroid cancer
                  • Decreased phosphate (8%)
                  • Fatigue (6%)
                  • Diarrhea (5%)
                  • Increased AST (4.3%)
                  • Increased ALT (3.6%)
                  • Decreased platelets (2.9%)
                  • Pyrexia (2.2%)
                  • Dyspnea (2.2%)
                  • Decreased sodium (2.2%)
                  • Decreased albumin (1.5%)
                  • Cough (1.4%)
                  • Increased potassium (1.4%)
                  • Increased bilirubin (1.4%)
                  • Increased alkaline phosphatase (1.4%)

                <1%

                Grade 3-4

                • NSCLC
                  • Cough (0.5%)
                • Thyroid cancer
                  • Musculoskeletal pain (0.7%)
                  • Constipation (0.7%)
                  • Abdominal pain (0.7%)
                  • Stomatitis (0.7%)
                  • Nausea (0.7%)
                  • Dizziness (0.7%)
                  • Decreased magnesium (0.7%)
                Previous
                Next:

                Warnings

                Contraindications

                None

                Cautions

                Severe, life-threatening, and fatal ILD/pneumonitis can occur; monitor for pulmonary symptoms indicative of ILD/pneumonitis

                Serious hepatic adverse reactions reported; monitor AST/ALT before initiation, every 2 weeks during first 2 months, and then monthly thereafter and as clinically indicated

                May cause serious, including fatal, hemorrhagic events

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

                Tumor lysis syndrome reported in MTC-treated patients; closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated

                Hypertension

                • Hypertension occurred; treatment-emergent hypertension was mostly managed with antihypertensive therapy
                • Do not initiate with uncontrolled hypertension
                • Optimize blood pressure (BP) before initiation
                • Monitor BP after 1 week, then at least monthly thereafter and as clinically indicated
                • Initiate or adjust antihypertensive therapy as needed

                Impaired wound healing

                • Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway
                • May have potential to adversely affect wound healing
                • Withhold for at least 5 days prior to elective surgery
                • Do not administer for at least 2 weeks following major surgery and until adequate wound healing
                • Safety of resumption after resolution of wound healing complications has not been established

                Drug interaction overview

                • Pralsetinib is a CYP3A4 and P-gp substrate
                • Strong CYP3A4 inhibitors
                  • Avoid coadministration
                  • Strong CYP3A inhibitors increase exposure and risk of toxicities to pralsetinib
                • Combined P-gp and strong CYP3A inhibitors
                  • Avoid coadministration; if unable to avoid, decrease pralsetinib dose
                  • Combined P-gp and strong CYP3A inhibitors increase plasma concentrations and effects of pralsetinib
                • Strong CYP3A4 inducers
                  • Avoid coadministration; if unable to avoid, increase pralsetinib dose
                  • Strong CYP3A inducers decrease exposure to pralsetinib
                Previous
                Next:

                Pregnancy & Lactation

                Pregnancy

                Based on animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females

                No data available on use in pregnant females to inform drug-associated risk

                Verify pregnancy status of females of reproductive potential before initiation

                Contraception

                • Females of reproductive potential: Use effective nonhormonal contraception during treatment and for 2 weeks after final dose; pralsetinib may render hormonal contraceptives ineffective
                • Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after final dose

                Infertility

                • Based on histopathological findings in male and female rats and a dedicated fertility study, fertility may be impaired

                Animal data

                • Oral pralsetinib administered to pregnant rats during organogenesis resulted in malformation and embryolethality at maternal exposures below human exposure at a dose of 400 mg qDay
                • Advise pregnant females of potential risk to fetus

                Lactation

                There are no data on presence of pralsetinib or its metabolites in human milk, effects on breastfed children, or on milk production

                Advise females not to breastfeed during treatment and for 1 week after 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.

                Previous
                Next:

                Pharmacology

                Mechanism of Action

                Selective inhibitor of rearranged during transfection (RET) alterations and resistant mutations; specifically designed to spare VEGFR2 and other kinases with the potential to drive off-target toxicity

                Exhibited antitumor activity in cultured cells and animal tumor implantation models harboring oncogenic RET fusions or mutations

                Absorption

                Peak plasma concentration: 2830 ng/mL (400-mg dose, fasted)

                Peak plasma time: 2-4 hr (single 60- to 600-mg dose)

                AUC: 43,900 ng⋅hr/mL (400-mg dose, fasted)

                Steady-state reached at 3-5 days

                Effects of food

                Administering with high-fat meal (ie, ~800-1000 calories with 50-60% of calories from fat) delayed peak concentration time and increased peak plasma concentration and AUC

                Single 400-mg dose

                • Mean peak plasma concentration increased by 104%
                • Mean AUC increased by 122%
                • Peak plasma time delayed from 4-8.5 hr

                Distribution

                Vd: 228 L

                Protein bound: 97.1%

                Blood-to-plasma ratio: 0.6-0.7

                Metabolism

                Primarily metabolized by CYP3A4 and to lesser extent by CYP2D6 and CYP1A2

                Following single oral dose of ~310 mg of radiolabeled pralsetinib to healthy individuals, metabolites from oxidation (M531, M453, M549b) and glucuronidation (M709) were detected as 5%

                Elimination

                Half-life: 14.7 hr (single dose); 22.2 hr (multiple doses)

                Clearance (steady-state): 9.1 L/hr

                Excretion: ~73% (urine; 66% unchanged); 6% (feces; 4.8% unchanged)

                Previous
                Next:

                Administration

                Oral Administration

                Take on empty stomach (no food intake for at least 2 hr before and 1 hr after dose)

                Missed dose: Take as soon as possible on same day; resume regular daily dose schedule thereafter

                Vomited dose: Do not take additional dose; continue with next scheduled dose

                Storage

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

                Previous
                Next:

                Images

                No images available for this drug.
                Previous
                Next:

                Patient Handout

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

                Formulary

                FormularyPatient Discounts

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

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

                Adding plans allows you to:

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

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

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

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

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

                Email Forms to Patient

                From:

                To:

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

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

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