Source: FDA, National Drug Code (US) Revision Year: 2020
GAVRETO is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Select patients for treatment with GAVRETO based on the presence of a RET gene fusion [see Clinical Studies (14)].
The recommended dosage of GAVRETO is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO) [see Clinical Pharmacology (12.3)]. Continue treatment until disease progression or until unacceptable toxicity.
If a dose of GAVRETO is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for GAVRETO the next day.
Do not take an additional dose if vomiting occurs after GAVRETO but continue with the next dose as scheduled.
The recommended dose reductions and dosage modifications for adverse reactions are provided in Table 1 and Table 2.
Table 1. Recommended Dose Reductions for GAVRETO for Adverse Reactions:
| Dose Reduction | Recommended Dosage |
|---|---|
| First | 300 mg once daily |
| Second | 200 mg once daily |
| Third | 100 mg once daily |
Permanently discontinue GAVRETO in patients who are unable to tolerate 100 mg taken orally once daily.
The recommended dosage modifications for adverse reactions are provided in Table 2.
Table 2. Recommended Dosage Modifications for GAVRETO for Adverse Reactions:
| Adverse Reaction | Severity* | Dosage Modification |
|---|---|---|
| ILD/Pneumonitis [see Warnings and Precautions (5.1)] | Grade 1 or 2 | Withhold GAVRETO until resolution. Resume by reducing the dose as shown in Table 1. Permanently discontinue GAVRETO for recurrent ILD/pneumonitis. |
| Grade 3 or 4 | Permanently discontinue for confirmed ILD/pneumonitis. | |
| Hypertension [see Warnings and Precautions (5.2)] | Grade 3 | Withhold GAVRETO for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled. |
| Grade 4 | Discontinue GAVRETO. | |
| Hepatotoxicity [see Warnings and Precautions (5.3)] | Grade 3 or Grade 4 | Withhold GAVRETO and monitor AST/ALT once weekly until resolution to Grade 1 or baseline. Resume at reduced dose (Table 1). If hepatotoxicity recurs at Grade 3 or higher, discontinue GAVRETO. |
| Hemorrhagic Events [see Warnings and Precautions (5.4)] | Grade 3 or Grade 4 | Withhold GAVRETO until recovery to baseline or Grade 0 or 1. Discontinue GAVRETO for severe or life-threatening hemorrhagic events. |
| Other Adverse Reactions [see Adverse Reactions 6.1] | Grade 3 or 4 | Withhold GAVRETO until improvement to ≤ Grade 2. Resume at reduced dose (Table 1). Permanently discontinue for recurrent Grade 4 adverse reactions. |
* Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03
Avoid coadministration of GAVRETO with known combined P-gp and strong CYP3A inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor cannot be avoided, reduce the current dose of GAVRETO as recommended in Table 3. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume GAVRETO at the dose taken prior to initiating the combined P-gp and strong CYP3A inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Table 3. Recommended Dosage Modifications for GAVRETO for Coadministration with Combined P-gp and Strong CYP3A Inhibitors:
| Current GAVRETO Dosage | Recommended GAVRETO Dosage |
|---|---|
| 400 mg orally once daily | 200 mg orally once daily |
| 300 mg orally once daily | 200 mg orally once daily |
| 200 mg orally once daily | 100 mg orally once daily |
Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration with a strong CYP3A inducer cannot be avoided, increase the starting dose of GAVRETO to double the current GAVRETO dosage starting on Day 7 of coadministration of GAVRETO with the strong CYP3A inducer. After the inducer has been discontinued for at least 14 days, resume GAVRETO at the dose taken prior to initiating the strong CYP3A inducer [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
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