IPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.5 Pharmacogenomics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, and Impairment ofFertility
14 CLINICAL STUDIES
14.1 Urothelial Carcinoma with Susceptible FGFRGenetic Alterations
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
BALVERSATM is indicated for the treatment of adult patients with locally advanced or metastaticurothelial carcinoma (mUC), that has:
•susceptible FGFR3 or FGFR2 genetic alterations, and
•progressed during or following at least one line of prior platinum-containing chemotherapy,including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA [seeDosage and Administration (2.1) and Clinical Studies (14)].
This indication is approved under accelerated approval based on tumor response rate. Continuedapproval for this indication may be contingent upon verification and description of clinical benefit inconfirmatory trials [see Clinical Studies (14)].
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients for the treatment of locally advanced or metastatic urothelial carcinoma withBALVERSA based on the presence of susceptible FGFR genetic alterations in tumor specimens asdetected by an FDA-approved companion diagnostic [see Clinical Studies (14.1)].
Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer isavailable at: http://www.fda.gov/CompanionDiagnostics.
2.2 Recommended Dosage and Schedule
The recommended starting dose of BALVERSA is 8 mg (two 4 mg tablets) orally once daily, with adose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels andtolerability 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, thenext dose should be taken the next day. Treatment should continue until disease progression orunacceptable toxicity occurs.
If a dose of BALVERSA is missed, it can be taken as soon as possible on the same day. Resume theregular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make upfor the missed dose.
Dose Increase based on Serum Phosphate Levels
Assess serum phosphate levels 14 to 21 days after initiating treatment. Increase the dose of BALVERSAto 9 mg once daily if serum phosphate level is < 5.5 mg/dL and there are no ocular disorders or Grade 2or greater adverse reactions. Monitor phosphate levels monthly for hyperphosphatemia [seePharmacodynamics (12.2)].
2.3 Dose Modifications for Adverse Reactions
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
t |
