Usual Adult Dose for Cholangiocarcinoma of biliary tract

13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles

Duration of therapy: Until disease progression or unacceptable toxicity occurs.

Comments:

• FGFR 2 fusion positivity status must be known prior to initiation of therapy.
• Assessment for FGFR 2 fusion positivity in tumor specimen should be performed with an appropriate diagnostic test.
• This indication is approved under accelerated approval based on overall response rate and duration of response.

Use: For the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test

Usual Adult Dose for Lymphoma

13.5 mg orally once daily

Duration of therapy: Until disease progression or unacceptable toxicity occurs.

Comments:

• FGFR 1 rearrangement positivity status must be known prior to the initiation of therapy.
• Assessment for FGFR 1 rearrangement positivity in tumor specimen should be performed with an appropriate diagnostic test.

Use: For the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement

Usual Adult Dose for Multiple Myeloma

13.5 mg orally once daily

Duration of therapy: Until disease progression or unacceptable toxicity occurs.

Comments:

• FGFR 1 rearrangement positivity status must be known prior to the initiation of therapy.
• Assessment for FGFR 1 rearrangement positivity in tumor specimen should be performed with an appropriate diagnostic test.

Use: For the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement

Renal Dose Adjustments

Mild or moderate renal dysfunction (CrCl greater than 30 to less than 90 mL/min): No adjustment recommended.
Severe renal dysfunction (CrCl less than 30 mL/min):

• Cholangiocarcinoma:
• 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles
• Myeloid/lymphoid neoplasms:
• 9 mg orally once daily

Liver Dose Adjustments

Mild (total bilirubin greater than the upper limit of normal (ULN) to 1.5 x ULN or AST greater than ULN) or moderate hepatic dysfunction (total bilirubin Greater than 1.5 to 3 × ULN with any AST): No adjustment recommended.
Severe hepatic dysfunction (total bilirubin greater than 3 x ULN with any AST):

• Cholangiocarcinoma:
• 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles
• Myeloid/lymphoid neoplasms:
• 9 mg orally once daily

Dose Adjustments

GENERAL RECOMMENDED DOSE MODIFICATION SCHEDULE FOR ADVERSE REACTIONS:

• Cholangiocarcinoma with FGFR2 Fusion or Rearrangement:
• First dose reduction: 9 mg once daily for first 14 days of each 21-day cycle
• Second dose reduction: 4.5 mg once daily for first 14 days of each 21-day cycle
• Permanently discontinue this drug if unable to tolerate 4.5 mg once daily.

• Myeloid/lymphoid neoplasms with FGFR1 Rearrangement:
• First dose reduction: 9 mg once daily
• Second dose reduction: 4.5 mg once daily
• Third dose reduction: 4.5 mg once daily for first 14 days of each 21-day cycle
• Permanently discontinue this drug if unable to tolerate 4.5 mg once daily for first 14 days of each 21-day cycle.

DOSE MODIFICATION FOR SPECIFIC ADVERSE REACTIONS:
RETINAL PIGMENT EPITHELIAL DETACHMENT (RPED):

• If asymptomatic and stable on serial examination, continue this drug; if symptomatic or worsening on serial examination, withhold this drug; if asymptomatic and improved on subsequent examination, resume this drug at a lower dose; if symptoms persist or examination does not improve, consider permanent discontinuation of therapy.

HYPERPHOSPHATEMIA:

• Serum phosphate greater than 7 mg/dL to 10 mg/dL: Initiate phosphate lowering therapy and monitor serum phosphate weekly; withhold this drug if levels are not less than 7 mg/dL within 2 weeks of starting phosphate lowering therapy; resume this drug at the same dose when phosphate levels are less than 7 mg/dL for first occurrence; resume at a lower dose level for subsequent recurrences.
• Serum phosphate greater than 10 mg/dL: Initiate phosphate lowering therapy and monitor serum phosphate weekly; withhold therapy if levels are not 10 mg/dL or less within 1 week after starting phosphate lowering therapy; resume therapy at the next lower dose level when phosphate levels are less than 7 mg/dL; Permanently discontinue therapy for recurrence of serum phosphate more than 10 mg/dL following 2 dose reductions.

OTHER ADVERSE REACTIONS:

• GRADE 3: Withhold therapy until resolves to Grade 1 or baseline; resume therapy at next lower dose if resolves within 2 weeks; permanently discontinue therapy if does not resolve within 2 weeks; permanently discontinue therapy for recurrent Grade 3 after 2 dose reductions.
• GRADE 4: Permanently discontinue therapy.

DOSE MODIFICATION FOR CONCOMITANT USE WITH STRONG OR MODERATE CYP450 3A INHIBITORS:
Avoid concomitant use of strong and moderate CYP450 3A inhibitors with this drug. If concomitant use with a strong or moderate CYP450 3A inhibitor cannot be avoided:

• Reduce this drug dose from 13.5 mg to 9 mg.
• Reduce this drug dose from 9 mg to 4.5 mg.
• If concomitant use of a strong or moderate CYP450 3A inhibitor is discontinued, increase this drug dose (after 3 plasma half-lives of the CYP450 3A inhibitor) to the dose that was used before starting the strong inhibitor.

Precautions

CONTRAINDICATIONS:

• None

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

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: No adjustment recommended.

Other Comments

Administration advice:

• Take this drug with or without food at approximately the same time every day.
• Swallow tablets whole; do not crush, chew, split, or dissolve tablets.
• If the patient misses a dose by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose.

Storage requirements:

• Store this drug at room temperature 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59°F to 86F).

Monitoring:

• Serum phosphate: Monitor weekly

Patient advice:

• Females should be advised not to breastfeed during therapy and for 1 week after.
• Advise females of reproductive potential to use effective contraception during therapy and for 1 week after.
• Advise males with female partners of reproductive potential to use effective contraception during therapy and for 1 week.
• Advise patients to avoid eating grapefruit or drinking grapefruit juice while taking this drug.
• Advise patients to use ocular demulcents, in order to prevent or treat dry eye.
• Advise patients that this drug may cause nail disorders.
• Advise patients that this drug may cause ocular toxicities.
• Advise patients to immediately report to the healthcare provider any symptoms of muscle cramps, numbness, or tingling around the mouth.