Active Ingredient: Erdafitinib
Erdafitinib as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC), harbouring susceptible FGFR3 genetic alterations who have previously received at least one line of therapy containing a PD-1 or PD-L1 inhibitor in the unresectable or metastatic treatment setting.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 8 milligrams erdafitinib, once daily.
The recommended starting dose of erdafitinib is 8 mg orally once daily. This dose should be maintained and serum phosphate level should be assessed between 14 and 21 days after initiating treatment. Up-titrate the dose to 9 mg once daily if the serum phosphate level is <9.0 mg/dL (<2.91 mmol/L), and there is no drug-related toxicity. If the phosphate level is 9.0 mg/dL or higher follow the relevant dose modifications in Table 2. After day 21 the serum phopshate level should not be used to guide up-titration decision.
If vomiting occurs any time after taking erdafitinib, the next dose should be taken the next day.
Treatment should continue until disease progression or unacceptable toxicity occurs.
If a dose of erdafitinib is missed, it can be taken as soon as possible. The regular daily dose schedule for erdafitinib should be resumed the next day. Extra tablets should not be taken to make up for the missed dose.
Table 1. Erdafitinib dose reduction schedule:
| Dose | 1st dose reduction | 2nd dose reduction | 3rd dose reduction | 4th dose reduction | 5th dose reduction |
|---|---|---|---|---|---|
| 9 mg (e.g., three 3 mg tablets) | 8 mg (e.g., two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
| 8 mg (e.g., two 4 mg tablets) | 6 mg (two 3 mg tablets) | 5 mg (one 5 mg tablet) | 4 mg (one 4 mg tablet) | Stop |
Hyperphosphataemia is an expected, transient pharmacodynamic effect of FGFR inhibitors. Phosphate concentrations should be assessed prior to the first dose and then monitored monthly. For elevated phosphate concentrations in patients treated with erdafitinib dose modification guidelines in Table 2 should be followed. For persistently elevated phosphate concentrations, adding a non-calcium containing phosphate binder (e.g., sevelamer carbonate) should be considered as needed (see Table 2).
Table 2. Recommended dose modifications based on serum phosphate concentrations with the use of erdafitinib after up-titration:
| Serum phosphate concentration | Erdafitinib management |
|---|---|
| For phosphate concentrations >5.5 mg/dL, restrict phosphate intake to 600-800 mg/day. | |
| <6.99 mg/dL (<2.24 mmol/L) | Continue erdafitinib at current dose. |
| 7.00-8.99 mg/dL (2.25-2.90 mmol/L) | Continue erdafitinib treatment. Start phosphate binder with food until phosphate level is <7.00 mg/dL. A dose reduction should be implemented for a sustained serum phosphate level of ≥7.00 mg/dL for a period of 2 months or in the presence of additional adverse events or additional electrolyte disturbances linked to prolonged hyperphosphataemia. |
| 9.00-10.00 mg/dL (>2.91-3.20 mmol/L) | Withhold erdafitinib treatment until serum phosphate level returns to <7.00 mg/dL (weekly testing recommended). Start phosphate binder with food until serum phosphate level returns to <7.00 mg/dL. Re-start treatment at the same dose level (see Table 1). A dose reduction should be implemented for sustained serum phosphate level of ≥9.00 mg/dL for a period of 1 month or in the presence of additional adverse events or additional electrolyte disturbances linked to prolonged hyperphosphataemia. |
| >10.00 mg/dL (>3.20 mmol/L) | Withhold erdafitinib treatment until serum phosphate level returns to <7.00 mg/dL (weekly testing recommended). Re-start treatment at the first reduced dose level (see Table 1). If serum phosphate level of ≥10.00 mg/dL is sustained for >2 weeks, erdafitinib should be discontinued permanently. Medical management of symptoms as clinically appropriate. |
| Significant alteration from baseline renal function or Grade 3 hypocalcaemia due to hyperphosphataemia. | Erdafitinib should be discontinued permanently. Medical management as clinically appropriate. |
No specific dose adjustments are considered necessary for elderly patients. Limited data are available in patients older than 85 years old.
Erdafitinib should be taken with or without food at about the same time each day.
Grapefruit or Seville oranges should be avoided due to strong CYP3A4 inhibition.
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