Usual Adult Dose for Urothelial Carcinoma

8 mg orally once daily; increase to 9 mg orally once daily based on serum phosphate levels and tolerability at 14 to 21 days until disease progression or unacceptable toxicity

Comments

• Select patients for therapy based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic.

Use: For the treatment of adult patients with locally advanced or metastatic urothelial 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.

Renal Dose Adjustments

Mild to moderate renal impairment: No adjustment recommended.
Severe renal impairment: Data not available

Liver Dose Adjustments

Mild to moderate hepatic impairment: No adjustment recommended.
Severe hepatic impairment: Data not available

Dose Adjustments

DOSE REDUCTION SCHEDULE FOR ADVERSE REACTIONS:
9 MG DOSE SCHEDULE:

• First dose reduction: 8 mg
• Second dose reduction: 6 mg
• Third dose reduction: 5 mg
• Fourth dose reduction: 4 mg
• Fifth dose reduction: Stop

8 MG DOSE SCHEDULE:

• First dose reduction: 6 mg
• Second dose reduction: 5 mg
• Third dose reduction: 4 mg
• Fourth dose reduction: Stop

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
HYPERPHOSPHATEMIA (NOTE: Restrict phosphate intake in all patients to 600 to 800 mg daily; if serum phosphate is above 7 mg/dL consider adding an oral phosphate binder until serum phosphate level returns to less than 5.5 mg/dL):

• Phosphate 5.6 to 6.9 mg/dL (1.8 to 2.3 mmol/L): Continue at current dose
• Phosphate 7 to 9 mg/dL (2.3 to 2.9 mmol/L): Withhold therapy with weekly reassessments until level returns to less than 5.5 mg/dL (or baseline); restart at the same dose level; dose may be reduced for hyperphosphatemia lasting longer than 1 week
• Phosphate greater than 9 mg/dL (greater than 2.9 mmol/L): Withhold therapy with weekly reassessments until level returns to less than 5.5 mg/dL or baseline; restart at 1 dose level lower
• Phosphate greater than 10 mg/dL (greater than 3.2 mmol/L) or significant alteration in baseline renal function or Grade 3 hypercalcemia: Withhold therapy with weekly reassessments until level returns to less than 5.5 mg/dL or baseline; restart at 2 dose levels lower

CENTRAL SEROUS RETINOPATHY/RETINAL PIGMENT EPITHELIAL DETACHMENT (CSR/RPED):

• Grade 1 (asymptomatic; clinical or diagnostic observations only): Withhold therapy 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 less than or equal to 3 lines of decreased vision from baseline: Withhold therapy until resolution; if resolves within 4 weeks resume at the next lower dose level
• Grade 3: Visual acuity worse than 20/40 or greater than 3 lines of decreased vision from baseline: Withhold therapy until resolution; if resolves within 4 weeks resume 2 dose levels lower; if recurs, consider permanent discontinuation of therapy
• Grade 4: (visual acuity 20/200 or worse in affected eye): Permanently discontinue therapy.

OTHER ADVERSE REACTIONS:

• Grade 3: Withhold therapy until resolves to Grade 1 or baseline; resume 1 dose level lower
• Grade 4: Permanently discontinue therapy.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Tablets should be swallowed whole, not broken, crushed, or divided.
• If vomiting occurs any time after taking this drug, take the next dose the next day.
• If a dose is missed, take the missed as soon as possible. Resume the regular daily dose schedule the next day. Extra tablets should not be taken to make up for the missed dose.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F).

Patient advice:

• Read the approved patient labeling each time you fill this drug.
• Contact your healthcare provider immediately if you experience any visual changes.