Erdafitinib

Erdafitinib is a kinase inhibitor indicated for locally advanced or metastatic urothelial carcinoma that has fibroblast growth factor receptor-2 (FGFR2) or FGFR3 genetic alterations and progressed during or following at least 1 line of prior platinum-containing chemotherapy.

The recommended starting dose is 8 mg PO once daily, with a dose increase to 9 mg PO once daily based on serum phosphate levels and tolerability at 14-21 days. Treatment should be continued until disease progression or unacceptable toxicity occurs.

• Locally Advanced or Metastatic Urothelial Carcinoma: Indicated for adult patients with susceptible FGFR3 or FGFR2 genetic alterations who have progressed during or following at least one line of prior platinum-containing chemotherapy.

Cytotoxic Chemotherapy

FGFR Kinase Inhibitor

Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2. It inhibits FGFR phosphorylation and signaling and decreases cell viability in cell lines expressing FGFR genetic alterations.

Fibroblast growth factor receptor (FGFR) inhibitor; FGFRs are a family of receptor tyrosine kinases. In vitro, erdafitinib inhibits FGFR phosphorylation and signaling and decreases cell viability in cell lines expressing FGFR genetic alterations.

Adult Dose:

• Urothelial Carcinoma: Initial: 8 mg PO qDay; increase to 9 mg PO qDay based on serum phosphate levels and tolerability at 14-21 days.
• Mild Hepatic Impairment: No dosage adjustment needed.
• Moderate Hepatic Impairment: No dosage adjustment needed.
• Severe Hepatic Impairment: Unknown.

Renal Dose:

• Mild or Moderate Renal Impairment (eGFR 30-89 mL/min/1.73 m²): No dosage adjustment needed.
• Severe or Dialysis: Unknown.

Take this medicine orally as advised by your doctor. Swallow the tablet whole. Do not chew, crush or break it.

If you miss a dose of Erdafitinib, take it as soon as possible on the same day. Resume the regular daily dose schedule the next day. Do not take extra tablets to make up for the missed dose.

Common Side Effects (≥20%):

• Phosphate increased (76%)
• Stomatitis (56%)
• Fatigue (54%)
• Creatinine increased (52%)
• Diarrhea (47%)
• Dry mouth (45%)
• ALT increased (41%)
• Alkaline phosphatase increased (41%)
• Onycholysis (41%)
• Sodium decreased (40%)
• Decreased appetite (38%)
• Albumin decreased (37%)
• Dysgeusia (37%)
• Hemoglobin decreased (35%)
• Dry skin (34%)
• AST increased (30%)
• Magnesium decreased (30%)
• Constipation (28%)
• Dry eye (28%)
• Palmar-plantar erythrodysesthesia (26%)
• Alopecia (26%)
• Phosphate decreased (24%)
• Abdominal pain (23%)
• Calcium increased (22%)
• Nausea (21%)
• Musculoskeletal pain (20%)

Precautions:

• Ocular Disorders: Can cause central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED). Perform monthly ophthalmological examinations during first 4 months, then every 3 months, and urgently at any time for visual symptoms.
• Hyperphosphatemia: Increases in serum phosphate levels are a pharmacodynamic effect. Monitor and manage with dose modifications when required. Patients may require phosphate binders.
• Embryo-fetal Toxicity: Can cause fetal harm when administered to pregnant women. Advise patients to use effective contraception.
• Dry Eye Symptoms: Common; all patients should receive dry eye prophylaxis with ocular demulcents as needed.

Contraindications: Hypersensitivity.

Drug Interactions:

• Strong CYP2C9 or CYP3A4 Inhibitors: Increase erdafitinib plasma concentrations; avoid or consider lower dose.
• Strong CYP2C9 or CYP3A4 Inducers: Decrease erdafitinib efficacy; avoid coadministration.
• Moderate CYP2C9 or CYP3A4 Inducers: May decrease efficacy; dose may be increased up to 9 mg.
• Serum Phosphate Level-altering Agents: Avoid before initial dose modification period.
• CYP3A4 Substrates: Avoid coadministration with sensitive CYP3A4 substrates with narrow therapeutic indices.

Food Interactions: It is not known whether it is safe to consume alcohol with Erdafitinib. Consult your doctor.

Use in Pregnancy: Based on mechanism of action and animal studies, can cause fetal harm when administered to pregnant women. Pregnancy testing recommended. Advise females to use effective contraception during treatment and for 1 month after last dose.

Use in Lactation: No data are available on presence in human milk, effects on breastfed children, or on milk production. Advise lactating women not to breastfeed during treatment and for 1 month following last dose.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between elderly and younger patients.

Renal Impairment: No dose adjustment recommended for patients with mild to moderate renal impairment (eGFR 30-89 mL/min/1.73 m²). Severe or dialysis: Unknown.

Hepatic Impairment: No dose adjustment recommended for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Severe (Child-Pugh C): Limited data available.

Overdose: Limited experience with overdosage. In case of overdose, symptomatic treatment should be given and seek immediate medical attention.

Storage: Store below 30°C in a cool and dry place. Keep away from light. Keep out of reach of children.

Erdafitinib