Retevmo

• 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.

• 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.

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

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

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

Dosage Modification for Severe Hepatic Impairment

Reduce the recommended dosage of Retevmo for patients with severe hepatic impairment as recommended in Table 4.

Table 3: Recommended Retevmo Dosage for Severe Hepatic Impairment

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.

• 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.