Dosing and Administration

Patient selection1

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)].

Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: http://www.fda.gov/CompanionDiagnostics.

Administration1

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No fasting restrictions. Tablets can be taken with or without food

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Tablets should be swallowed whole

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Missed doses should be taken as soon as possible on the same day and the regular daily dose taken on the next day; extra tablets should not be taken to make up for the missed dose

Dosing and dose adjustments overview1

For full Dosing and Dose Modification, please refer to section 2 of the full BALVERSA® Prescribing Information.

BALVERSA dosing and dose adjustment guide

*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. Treatment should continue until disease progression or unacceptable toxicity occurs.

Dose modifications and drug interactions1

For coadministration with moderate CYP2C9 or strong CYP3A4 inhibitors, consider alternative agents or monitor closely for adverse reactions.

Avoid concomitant use of strong CYP2C9 or CYP3A4 inducers with BALVERSA®.

For coadministration with moderate CYP2C9 or CYP3A4 inducers, increase the BALVERSA® dose up to 9 mg.

Serum phosphate level-altering agents: Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose modification period.

CYP3A4 substrates: Avoid concomitant use with sensitive CYP3A4 substrates with narrow therapeutic indices.

OCT2 substrates: Consider alternative agents or consider reducing the dose of OCT2 substrates based on tolerability.

P-gp substrates: Separate BALVERSA® administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices.

Managing hyperphosphatemia1

Increases in phosphate levels are a pharmacodynamic effect of BALVERSA®. Hyperphosphatemia was reported as an adverse reaction in 76% of patients treated with BALVERSA®. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8–116) after initiating BALVERSA®. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA®.

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.

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) of the full Prescribing Information].

Monitor for hyperphosphatemia and follow the dose modification guidelines when required.

Dose modifications for hyperphosphatemia

Adverse Reaction BALVERSA® Dose Modification
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.

Please see full BALVERSA® Prescribing Information for dose modifications for elevated phosphate levels.

Managing eye disorders1

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography.

Withhold BALVERSA® when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 severity.

Dose modifications for CSR/RPED1

For 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.

For 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.

For 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.

For Grade 4: Visual acuity 20/200 or worse in affected eye

Permanently discontinue BALVERSA®.

Please see Safety and full BALVERSA® Prescribing Information for additional recommendations on managing potential eye disorders.

CSR = central serous retinopathy; RPED = retinal pigment epithelial detachment.

Managing other adverse reactions1

Dose modifications for other adverse reactions1

Adverse Reaction BALVERSA® Dose Modification
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).

For detailed information on the management of adverse reactions, please see the full BALVERSA® Prescribing Information.

Embryo-fetal exposure1

BALVERSA® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose.

Reference

1. BALVERSA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.