Source: FDA, National Drug Code (US) Revision Year: 2020
BALVERSA is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC), that has:
Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA [see Dosage and Administration (2.1) and Clinical Studies (14)].
This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14)].
Select patients for the treatment of locally advanced or metastatic urothelial carcinoma with BALVERSA based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic [see Clinical Studies (14.1)].
The recommended starting dose of BALVERSA is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels and tolerability at 14 to 21 days [see Dosage and Administration (2.3)].
Swallow tablets whole with or without food. If vomiting occurs any time after taking BALVERSA, the next dose should be taken the next day. Treatment should continue until disease progression or unacceptable toxicity occurs.
If a dose of BALVERSA is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose.
Assess serum phosphate levels 14 to 21 days after initiating treatment. Increase the dose of BALVERSA to 9 mg once daily if serum phosphate level is <5.5 mg/dL and there are no ocular disorders or Grade 2 or greater adverse reactions. Monitor phosphate levels monthly for hyperphosphatemia [see Pharmacodynamics (12.2)].
The recommended dose modifications for adverse reactions are listed in Table 1.
Table 1. BALVERSA Dose Reduction Schedule:
| Dose | 1st dose reduction | 2nd dose reduction | 3rd dose reduction | 4th dose reduction | 5th dose reduction |
|---|---|---|---|---|---|
| 9 mg (three 3 mg tablets) | 8 mg (two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
| 8 mg (two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
Table 2 summarizes recommendations for dose interruption, reduction, or discontinuation of BALVERSA in the management of specific adverse reactions.
Table 2. Dose Modifications for Adverse Reactions:
| Adverse Reaction | BALVERSA Dose Modification |
|---|---|
| Hyperphosphatemia | |
| In all patients, restrict phosphate intake to 600-800 mg daily. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <5.5 mg/dL. | |
| 5.6-6.9 mg/dL (1.8–2.3 mmol/L) | Continue BALVERSA at current dose. |
| 7.0-9.0 mg/dL (2.3–2.9 mmol/L) | Withhold BALVERSA with weekly reassessments until level returns to < 5.5 mg/dL (or baseline). Then restart BALVERSA at the same dose level. A dose reduction may be implemented for hyperphosphatemia lasting >1 week. |
| > 9.0 mg/dL (>2.9 mmol/L) | Withhold BALVERSA with weekly reassessments until level returns to <5.5 mg/dL (or baseline). Then may restart BALVERSA at 1 dose level lower. |
| >10.0 mg/dL (>3.2 mmol/L) or significant alteration in baseline renal function or Grade 3 hypercalcemia | Withhold BALVERSA with weekly reassessments until level returns to <5.5 mg/dL (or baseline). Then may restart BALVERSA at 2 dose levels lower. |
| Central Serous Retinopathy/Retinal Pigment Epithelial Detachment (CSR/RPED) | |
| Grade 1: Asymptomatic; clinical or diagnostic observations only | Withhold until resolution. If resolves within 4 weeks, resume at the next lower dose level. Then, if no recurrence for a month, consider re-escalation. If stable for 2 consecutive eye exams but not resolved, resume at the next lower dose level. |
| Grade 2: Visual acuity 20/40 or better or ≤3 lines of decreased vision from baseline | Withhold until resolution. If resolves within 4 weeks, may resume at the next lower dose level. |
| Grade 3: Visual acuity worse than 20/40 or >3 lines of decreased vision from baseline | Withhold until resolution. If resolves within 4 weeks, may resume two dose levels lower. If recurs, consider permanent discontinuation. |
| Grade 4: Visual acuity 20/200 or worse in affected eye | Permanently discontinue. |
| Other Adverse Reactions* | |
| Grade 3 | Withhold BALVERSA until resolves to Grade 1 or baseline, then may resume dose level lower. |
| Grade 4 | Permanently discontinue. |
* Dose adjustment graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv4 .03).
Store at 20°C-25°C (68°F-77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
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