Retevmo (selpercatinib): Cancer Treatment Warnings

Generic drug: selpercatinib

Brand name: Retevmo

What is Retevmo (selpercatinib), and how does it work?

Retevmo (selpercatinib) is a prescription medicine that is used to treat certain cancers caused by abnormal RET genes in:

adults with non-small cell lung cancer (NSCLC) that has spread.
adults and children 12 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread who require a medicine by mouth or injection (systemic therapy).
adults and children 12 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy) and who have received radioactive iodine and it did not work or is no longer working.

Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if Retevmo is safe and effective in children younger than 12 years of age.

What are the side effects of Retevmo?

The most common side effects of Retevmo include:

increased levels of liver enzymes
increased blood sugar levels
decrease in white blood cell count
decreased protein levels (albumin) in the blood
decreased levels of calcium in the blood
dry mouth
diarrhea
increased creatinine (kidney function test)
high blood pressure
tiredness
swelling of your arms, legs, hands, and feet (peripheral edema)
decrease in platelet count
increased cholesterol levels
rash
decreased levels of salt (sodium) in the blood
constipation

Retevmo may affect fertility in females and males, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

These are not all the possible side effects with Retevmo.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Retevmo?

Patient Selection

Select patients for treatment with Retevmo based on
the presence of a RET gene fusion (NSCLC or thyroid cancer) or specific RET gene
mutation (MTC) in tumor specimens or plasma. An FDA-approved test for the detection of RET gene fusions and RET gene mutations is not currently available.

Important Administration Instructions

Retevmo may be taken with or without food unless coadministrated with a proton
pump inhibitor (PPI).

Recommended Dosage

The recommended dosage of
Retevmo based on body weight is:

Less than 50 kg: 120 mg
50 kg or greater: 160 mg

Take
Retevmo orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity.

Swallow the capsules whole. Do not crush or chew the capsules.

Do not take a missed dose unless it is more than 6 hours until next scheduled dose.

If vomiting occurs after
Retevmo administration, do not take an additional dose and continue to the next scheduled time for the next dose.

Dosage Modifications For Concomitant Use Of Acid-Reducing Agents

Avoid concomitant use of a PPI, a histamine-2 (H2) receptor antagonist, or a
locally-acting antacid with Retevmo. If concomitant use cannot be avoided:

Take
Retevmo with food when coadministered with a PPI.
Take Retevmo 2 hours before or 10 hours after administration of an H2 receptor antagonist.
Take
Retevmo 2 hours before or 2 hours after administration of a locally-acting antacid.

Dosage Modifications For Adverse Reactions

The recommended dose reductions for adverse reactions are provided in Table 1.

Table 1: Recommended
Retevmo Dose Reductions for Adverse Reactions

Dose ReductionPatients Weighing Less Than 50 kgPatients Weighing 50 kg or GreaterFirst80 mg orally twice daily120 mg orally twice dailySecond40 mg orally twice daily80 mg orally twice dailyThird40 mg orally once daily40 mg orally twice daily

Permanently discontinue
Retevmo in patients unable to tolerate three dose reductions.

The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended
Retevmo Dosage Modifications for Adverse Reactions

Adverse ReactionSeverityDosage ModificationHepatotoxicityGrade 3 or Grade 4

Withhold
Retevmo and monitor AST/ALT once weekly until resolution to Grade 1 or baseline.
Resume at reduced dose by 2 dose levels and monitor AST and 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 prior to the onset of Grade 3 or 4 increased AST or ALT after a minimum of 4 weeks without recurrence.

HypertensionGrade 3

Withhold
Retevmo for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled.

Grade 4

Discontinue Retevmo.

QT Interval Prolongation Grade 3

Withhold Retevmo until recovery to baseline or Grade 0 or 1.
Resume at a reduced dose.

Grade 4

Discontinue Retevmo

Hemorrhagic Events Grade 3 or Grade 4

Withhold Retevmo until recovery to baseline or Grade 0 or 1.
Discontinue
Retevmo for severe or life-threatening hemorrhagic events.

Hypersensitivity ReactionsAll Grades

Withhold
Retevmo until resolution of the event. Initiate corticosteroids.
Resume at a reduced dose by 3 dose levels while continuing corticosteroids.
Increase dose by 1 dose level each week until the dose taken prior to the onset of hypersensitivity is reached, then taper corticosteroids.

Dosage Modifications For Concomitant Use Of Strong And Moderate CYP3A Inhibitors

Avoid concomitant use of strong and moderate CYP3A inhibitors with
Retevmo. If
concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided,
reduce the Retevmo dose as recommended in Table 3. After the inhibitor has been
discontinued for 3 to 5 elimination half-lives, resume Retevmo at the dose taken
prior to initiating the CYP3A inhibitor.

Table 2: Recommended
Retevmo Dosage for Concomitant Use of Strong and Moderate CYP3A Inhibitors

Current
Retevmo DosageRecommended Retevmo DosageModerate CYP3A InhibitorStrong CYP3A Inhibitor120 mg orally twice daily80 mg orally twice daily40 mg orally twice daily160 mg orally twice daily120 mg orally twice daily80 mg orally twice daily

Dosage Modification For Severe Hepatic Impairment

Reduce the recommended dosage of
Retevmo for patients with severe hepatic impairment as recommended in Table 4 [see Use In Specific Populations].

Table 3: Recommended
Retevmo Dosage for Severe Hepatic Impairment

Current
Retevmo DosageRecommended Retevmo Dosage120 mg orally twice daily80 mg orally twice daily160 mg orally twice daily80 mg orally twice daily

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What drugs interact with Retevmo?

Effects Of Other Drugs On Retevmo

Acid-Reducing Agents

Concomitant use of Retevmo with acid-reducing agents decreases
selpercatinib plasma concentrations, which may reduce Retevmo anti-tumor activity.
Avoid concomitant use of PPIs, H2 receptor antagonists, and
locally-acting antacids with Retevmo. If coadministration cannot be avoided,
take Retevmo with food (with a PPI) or modify its administration time (with
a H2 receptor antagonist or a locally-acting antacid).

Strong And Moderate CYP3A Inhibitors

Concomitant use of Retevmo with a strong or moderate CYP3A inhibitor
increases selpercatinib plasma concentrations, which may increase the risk of
Retevmo adverse reactions, including QTc interval prolongation.
Avoid concomitant use of strong and moderate CYP3A inhibitors with
Retevmo. If concomitant use of strong and moderate CYP3A inhibitors cannot
be avoided, reduce the Retevmo dosage and monitor the QT interval with ECGs
more frequently.

Strong And Moderate CYP3A Inducers

Concomitant use of Retevmo with a strong or moderate CYP3A inducer
decreases selpercatinib plasma concentrations, which may reduce Retevmo anti-tumor activity.
Avoid coadministration of strong or moderate CYP3A inducers with
Retevmo.

Effects Of Retevmo On Other Drugs

CYP2C8 And CYP3A Substrates

Retevmo is a moderate CYP2C8 inhibitor and a weak CYP3A inhibitor.
Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases
their plasma concentrations, which may increase the risk of adverse reactions related to these substrates.
Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions.
If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.

Drugs That Prolong QT Interval

Retevmo is associated with QTc interval prolongation.
Monitor the QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong the QT interval.

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Is Retevmo safe to use while pregnant or breastfeeding?

Based on findings from animal studies, and its mechanism of action,
Retevmo can cause fetal harm when administered to a pregnant woman.
There are no available data on Retevmo use in pregnant women to inform drug-associated risk.
There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production.
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with
Retevmo and for 1 week after the final dose.