Usual Adult Dose for Cholangiocarcinoma of biliary tract

125 mg (one 100 mg capsule and one 25 mg capsule) orally once a day for 21 days on 7 days off of a 28-day cycle

Comments:

• Continue treatment until disease progression or unacceptable toxicity.
• Select patients for the treatment of unresectable locally advanced or metastatic cholangiocarcinoma based on the presence of an FGFR2 fusion or rearrangement.
• Information on FDA-approved test(s) for the detection of FGFR2 fusions or rearrangements in cholangiocarcinoma is available at: http://www.fda.gov/CompanionDiagnostics.

Renal Dose Adjustments

• Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): 100 mg orally once a day for 21 days on 7 days off of a 28-day cycle
• Severe renal dysfunction (CrCl 15 to less than 30 mL/min): Data not available

Liver Dose Adjustments

• Mild liver dysfunction (total bilirubin greater than the upper limit of normal [ULN] to 1.5 × ULN or AST greater than ULN ): 100 mg orally once a day for 21 days on 7 days off of a 28-day cycle
• Moderate liver dysfunction (total bilirubin greater than 1.5 to 3 × ULN with any AST): 75 mg orally once a day for 21 days on 7 days off of a 28-day cycle
• Severe liver dysfunction (total bilirubin greater than 3 × ULN with any AST): Not established

Dose Adjustments

Dose Reduction for Adverse Reactions:

• First dose reduction: 100 orally once a day
• Second dose reduction: 75 mg orally once a day
• Third dose reduction: 50 mg orally once a day

• Continue treatment at the current dose and continue periodic ophthalmic evaluation.
• If resolved within 14 days, continue treatment at the current dose.
• If unresolved within 14 days, withhold treatment until resolved; then resume at previous dose or at a lower dose.

• Continue treatment at the current dose and start or adjust the phosphate binder dose according to clinical practice.
• Monitor serum phosphate weekly.
• Phosphate binder dosing should be held during the week off therapy each cycle (Days 22-28) and during dose interruptions for non-hyperphosphatemia adverse events.
• If serum phosphate greater than 7.5 mg/dL or single phosphate greater than 9 mg/dL independent of duration of dose of the phosphate lowering therapy:
• Withhold treatment until level returns to serum phosphate of 5.5 mg/dL or less.
• If serum phosphate greater than 7.5 mg/dL occurred for less than 7 days: Restart treatment at the same dose with maximal phosphate binder dosing.
• If serum phosphate greater than 7.5 mg/dL for greater than 7 days or if patient had a one-time serum phosphate of greater than 9 mg/dL: Resume treatment at the next lower dose level with maximal phosphate binder dosing.
• Serum phosphate with life-threatening consequences; urgent intervention indicated (e.g., dialysis): Permanently discontinue treatment.

• Grade 3: Withhold dose until resolved to Grade 1 or less, then resume at the next lower dose level. If not resolved within 14 days or less, permanently discontinue treatment.
• Grade 4: Permanently discontinue treatment.

• It is recommended to avoid the coadministration of a proton pump inhibitor (PPI), a histamine-2 (H2) receptor antagonist, or a locally-acting antacid.
• If H2-antagonist coadministration cannot be avoided it is recommended to separate the administration of this drug by 2 hours before or 10 hours after.
• If locally-acting antacid coadministration cannot be avoided it is recommended to separate the administration of this drug by 2 hours before or 2 hours after.

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:

• Take on an empty stomach at least 1 hour before or 2 hours after food.
• Swallow capsules whole with water.
• Do not crush, chew, or dissolve capsules.

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

• Monitor serum phosphate weekly.
• Monitor for eye toxicity at 1 month, at 3 months, and then every 3 months thereafter while on therapy.

• Advise the patient to read the FDA-approved patient labeling (Patient Information).
• Advise lactating women not to breastfeed during therapy and for at least 1 month after the last dose.
• Advise females of reproductive potential to use effective contraception during treatment with and for at least 1 month after the last dose.
• Advise males that are partnered with females of reproductive potential to use effective contraception during treatment with and for at least 1 month after the last dose.
• Advise patients that if a dose is missed and it has passed 4 hours or more or if vomiting, skip the dose and take the next scheduled dose at its regular time.
• Advise patients that this drug may cause nail disorders.
• Advise patients that this drug may cause ocular toxicity and to immediately inform their healthcare provider if they experience any visual changes.
• Advise patients to use artificial tear substitutes or hydrating or lubricating eye gels to prevent or treat dry eyes.
• Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, and herbal products.
• Advise patients that this drug may cause hyperphosphatemia and soft tissue mineralization and to immediately inform their healthcare provider of any symptoms related to acute changes in phosphate levels such as muscle cramps, numbness, or tingling around the mouth.
• Advise patients to avoid grapefruit products during treatment.