Active Ingredient: Futibatinib
Futibatinib monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 20 milligrams futibatinib, once daily.
The recommended starting dose is 20 mg futibatinib taken orally once daily.
If a dose of futibatinib is missed by more than 12 hours or vomiting occurs after taking a dose, an additional dose should not be taken, and treatment should be resumed with the next scheduled dose.
Treatment should be continued until disease progression or unacceptable toxicity.
In all patients, dietary restrictions that limit phosphate intake are recommended as part of hyperphosphatemia management. A phosphate-lowering therapy should be initiated when serum phosphate level is ≥5.5 mg/dL. If the serum phosphate level is >7 mg/dL, the dose of futibatinib should be modified based on the duration and severity of hyperphosphatemia (see Table 2). Prolonged hyperphosphatemia can cause soft tissue mineralization, including cutaneous calcification, vascular calcification, and myocardial calcification.
If futibatinib treatment is stopped or serum phosphate level falls below normal range, phosphate-lowering therapy and diet should be discontinued. Severe hypophosphatemia may present with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and hemolytic anemia.
Dose modifications or interruption of dosing should be considered for the management of toxicities.
The recommended dose reduction levels are provided in Table 1.
Table 1. Recommended futibatinib dose reduction levels:
| Dose | Dose reduction levels | |
| 20 mg taken orally once daily | First | Second |
| 16 mg taken orally once daily | 12 mg taken orally once daily | |
Treatment should be permanently discontinued if patient is unable to tolerate 12 mg futibatinib once daily.
Dose modifications for hyperphosphatemia are provided in Table 2.
Table 2. Dose modifications for hyperphosphatemia:
| Adverse reaction | Futibatinib dose modification |
| Serum phosphate ≥5.5 mg/dL - ≤7 mg/dL | • Initiate phosphate lowering therapy and monitor serum phosphate weekly • Futibatinib should be continued at current dose |
| Serum phosphate >7 mg/dL - ≤10 mg/dL | • Initiate/intensify phosphate lowering therapy and monitor serum phosphate weekly AND • Dose reduce futibatinib to next lower dose – If the serum phosphate resolves to ≤7.0 mg/dL within 2 weeks after dose reduction, continue at this reduced dose – If serum phosphate is not ≤7.0 mg/dL within 2 weeks, further reduce futibatinib to the next lower dose – If serum phosphate is not ≤7.0 mg/dL within 2 weeks after the second dose reduction, withhold futibatinib until serum phosphate is ≤7.0 mg/dL and resume at the dose prior to suspending |
| Serum phosphate >10 mg/dL | • Initiate/intensify phosphate lowering therapy and monitor serum phosphate weekly AND • Suspend futibatinib until phosphate is ≤7.0 mg/dL and resume futibatinib at the next lower dose • Permanently discontinue futibatinib if serum phosphate is not ≤7.0 mg/dL within 2 weeks following 2 dose reductions |
Dose modifications for serous retinal detachment are provided in Table 3.
Table 3. Dose modifications for serous retinal detachment:
| Adverse reaction | Futibatinib dose modification |
| Asymptomatic | • Continue futibatinib at current dose. Monitoring should be performed as described in section 4.4. |
| Moderate decrease in visual acuity (best corrected visual acuity 20/40 or better or ≤3 lines of decreased vision from baseline); limiting instrumental activities of daily living | • Withhold futibatinib. If improved on subsequent examination, futibatinib should be resumed at the next lower dose level. • If symptoms recur, persist or examination does not improve, permanent discontinuation of futibatinib should be considered based on clinical status. |
| Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or >3 lines decreased vision from baseline up to 20/200); limiting activities of daily living | • Withhold futibatinib until resolution. If improved on subsequent examination, futibatinib may be resumed at 2 dose levels lower. • If symptoms recur, persist or examination does not improve, permanent discontinuation of futibatinib should be considered based on clinical status. |
| Visual acuity worse than 20/200 in affected eye; limiting activities of daily living | • Permanent discontinuation of futibatinib should be considered based on clinical status. |
Dose modifications for other adverse reactions are provided in Table 4.
Table 4. Dose modifications for other adverse reactions:
| Other Adverse Reactions | Grade 3a | • Withhold futibatinib until toxicity resolves to Grade 1 or baseline, then resume futibatinib – for hematological toxicities resolving within 1 week, at the dose prior to suspending. – for other adverse reactions, at next lower dose. |
| Grade 4a | Permanently discontinue futibatinib |
a Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03).
Taken with or without food at about the same time each day.
Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.
