Source: FDA, National Drug Code (US) Revision Year: 2020
RETEVMO is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC).
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
RETEVMO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
RETEVMO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.3)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
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 [see Clinical Studies (14)]. An FDA-approved test for the detection of RET gene fusions and RET gene mutations is not currently available.
RETEVMO may be taken with or without food unless coadministered with a proton pump inhibitor (PPI) [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].
The recommended dosage of RETEVMO based on body weight is:
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.
Avoid concomitant use of a PPI, a histamine-2 (H2) receptor antagonist, or a locally-acting antacid with RETEVMO [see Drug Interactions (7.1)]. If concomitant use cannot be avoided:
The recommended dose reductions for adverse reactions are provided in Table 1.
Table 1. Recommended RETEVMO Dose Reductions for Adverse Reactions:
| Dose Reduction | Patients Weighing Less Than 50 kg | Patients Weighing 50 kg or Greater |
|---|---|---|
| First | 80 mg orally twice daily | 120 mg orally twice daily |
| Second | 40 mg orally twice daily | 80 mg orally twice daily |
| Third | 40 mg orally once daily | 40 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 Reaction | Severity | Dosage Modification |
|---|---|---|
| Hepatotoxicity [see Warnings and Precautions (5.1)] | Grade 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. |
| Hypertension [see Warnings and Precautions (5.2)] | Grade 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 [see Warnings and Precautions (5.3)] | Grade 3 | • Withhold RETEVMO until recovery to baseline or Grade 0 or 1. • Resume at a reduced dose. |
| Grade 4 | • Discontinue RETEVMO | |
| Hemorrhagic Events [see Warnings and Precautions (5.4)] | 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 Reactions [see Warnings and Precautions (5.5)] | All 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. |
| Other Adverse Reactions [see Adverse Reactions (6.1)] | Grade 3 or Grade 4 | • Withhold RETEVMO until recovery to baseline or Grade 0 or 1. • Resume at a reduced dose. |
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 [see Drug Interactions (7.1)].
Table 3. Recommended RETEVMO Dosage for Concomitant Use of Strong and Moderate CYP3A Inhibitors:
| Current RETEVMO Dosage | Recommended RETEVMO Dosage | |
|---|---|---|
| Moderate CYP3A Inhibitor | Strong CYP3A Inhibitor | |
| 120 mg orally twice daily | 80 mg orally twice daily | 40 mg orally twice daily |
| 160 mg orally twice daily | 120 mg orally twice daily | 80 mg orally twice daily |
Reduce the recommended dosage of RETEVMO for patients with severe hepatic impairment as recommended in Table 4 [see Use in Specific Populations (8.7)].
Table 4. Recommended RETEVMO Dosage for Severe Hepatic Impairment:
| Current RETEVMO Dosage | Recommended RETEVMO Dosage |
|---|---|
| 120 mg orally twice daily | 80 mg orally twice daily |
| 160 mg orally twice daily | 80 mg orally twice daily |
Store at 20°C to 25°C (68°F to 77°F); excursions between 15°C and 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature].
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