Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Taiho Pharma Netherlands B.V., Barbara Strozzilaan 201, ,1083HN Amsterdam, Netherlands
Lytgobi 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.
Lytgobi therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer.
Presence of FGFR2 gene fusions or rearrangements should be confirmed by an appropriate diagnostic test prior to initiation of Lytgobi therapy.
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 (see section 4.4).
If Lytgobi 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.
Co-administration of futibatinib with strong CYP3A4/P-gp inhibitors, such as itraconazole, should be avoided. If this is not possible, based on careful monitoring of tolerability, a futibatinib dose reduction to the next lower level should be considered.
Co-administration of futibatinib with strong or moderate CYP3A4/P-gp inducers, such as rifampicin, should be avoided (see sections 4.4 and 4.5). If this is not possible, gradually increasing the futibatinib dose based on careful monitoring of tolerability should be considered.
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).
No specific dose adjustment is required for elderly patients (≥65 years) (see section 5.1).
Dose adjustment is not required for patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min estimated by Cockcroft-Gault). There are no data in patients with severe renal impairment (CLcr <30 mL/min) or for patients with end-stage renal disease receiving intermittent haemodialysis and therefore no dosing recommendation can be made (see section 5.2).
No dose adjustment is required when administering futibatinib to patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment. However, there is no safety data in patients with severe hepatic impairment. (see section 5.2).
The safety and efficacy of futibatinib in children less than 18 years of age have not been established. No data are available.
Lytgobi is for oral use. The tablets should be taken with or without food at about the same time each day. The tablets should be swallowed whole to ensure that the full dose is administered.
There is no information on overdose of futibatinib.
4 years.
This medicinal product does not require any special storage conditions.
PVC/PCTFE laminated blisters with aluminium foil backing with one tablet per cavity. Each blister contains a 7-day supply of film-coated tablets sealed inside a folding cardboard wallet in the following three dose packs:
Not all pack sizes may be marketed.
No special requirements for disposal.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
