Erdafitinib

Approved Indications:

• Locally Advanced or Metastatic Urothelial Carcinoma (mUC):
  Erdafitinib is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations, and who have progressed during or following at least one line of platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-based treatment.

Clinically Accepted Off-Label Uses:

• Cholangiocarcinoma (Bile Duct Cancer): Investigated in cases with FGFR2 gene fusions or rearrangements.
• Glioblastoma and other solid tumors: Under clinical trials in FGFR-altered cases.

General Administration:

• Route: Oral (tablet)
• Recommended Starting Dose: 8 mg once daily.
• Dose Adjustment: Increase to 9 mg once daily if serum phosphate is <5.5 mg/dL on Days 14–21 and no ≥ Grade 2 toxicity.
• Treatment Duration: Continue until disease progression or unacceptable toxicity.

Special Populations:

• Hepatic Impairment:
• Mild impairment: No dosage adjustment needed.
• Moderate to severe: Use with caution; limited data available.
• Renal Impairment:
• Mild to moderate (CrCl ≥30 mL/min): No adjustment required.
• Severe (CrCl <30 mL/min): Use caution; insufficient data.
• Elderly: No specific dose adjustment required, but monitor closely.
• Pediatric Use: Safety and efficacy not established in individuals under 18 years.

Administration Instructions:

• Take once daily with or without food.
• Swallow tablets whole with water.
• Avoid taking with strong CYP3A4 inducers/inhibitors unless necessary.
• Monitor phosphate levels periodically during therapy.

Erdafitinib is a reversible tyrosine kinase inhibitor that targets fibroblast growth factor receptors (FGFR) 1–4. FGFRs are involved in cell proliferation, differentiation, and angiogenesis. Genetic alterations in FGFR (especially FGFR2 and FGFR3) are implicated in the pathogenesis of various cancers, including urothelial carcinoma. Erdafitinib blocks FGFR phosphorylation and downstream signaling pathways, leading to inhibition of tumor cell proliferation and induction of apoptosis in cancer cells dependent on FGFR signaling.

• Absorption:
• Oral bioavailability: ~100%
• Time to peak concentration (Tmax): ~2–5 hours
• Distribution:
• Volume of distribution: ~29 L
• Plasma protein binding: ~99.8%
• Metabolism:
• Metabolized primarily by CYP2C9 and CYP3A4 enzymes.
• Elimination:
• Elimination half-life: ~59–68 hours
• Excretion: Mainly via feces (~69%) and urine (~19%)
• Steady-State Concentration: Achieved within 15 days of daily dosing.

• Pregnancy:
• FDA Pregnancy Category: Not assigned under current FDA format.
• Summary: Erdafitinib may cause fetal harm based on its mechanism of action and animal studies. Avoid use during pregnancy. Effective contraception is recommended during treatment and for at least 1 month after the last dose.
• Lactation:
• Unknown if excreted in human milk.
• Due to potential serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 1 month after the last dose.

• Primary Class: Antineoplastic Agent
• Subclass: FGFR Tyrosine Kinase Inhibitor (Targeted Therapy)

• Known hypersensitivity to erdafitinib or any component of the formulation
• Severe hepatic impairment (caution due to lack of data)
• Concurrent use with strong CYP2C9/CYP3A4 inducers may reduce efficacy
• Pregnancy (due to fetal harm)

• Eye Toxicity:
• Risk of central serous retinopathy (CSR) or retinal pigment epithelial detachment (RPED).
• Perform regular ophthalmic exams during treatment.
• Hyperphosphatemia:
• Common and dose-limiting. Monitor serum phosphate levels frequently.
• Embryo-Fetal Toxicity:
• May cause fetal harm; ensure effective contraception.
• Tumor Lysis Syndrome (TLS):
• Rare but serious; monitor in patients with high tumor burden.
• CNS Effects:
• Monitor for dry mouth, dysgeusia, and cognitive disturbances.
• CYP Enzyme Interactions:
• Avoid concurrent use with strong CYP2C9/CYP3A4 modulators.

Common Side Effects:

• Gastrointestinal: Stomatitis, diarrhea, dry mouth
• Skin: Hand-foot syndrome, nail disorders, dry skin
• Eye: Dry eyes, blurred vision, central serous retinopathy
• Metabolic: Hyperphosphatemia, increased creatinine
• General: Fatigue, decreased appetite, dysgeusia

Serious Side Effects:

• Central serous retinopathy
• Tumor lysis syndrome
• Retinal detachment
• Severe hyperphosphatemia
• Hepatotoxicity
• Severe ocular toxicity

Onset & Severity:

• Ocular toxicities may occur within weeks of initiation.
• Hyperphosphatemia is often dose-dependent and occurs early in treatment.

• CYP2C9 and CYP3A4 Inhibitors:
• May increase erdafitinib exposure → increased risk of toxicity.
• CYP2C9 and CYP3A4 Inducers:
• May decrease erdafitinib plasma levels → reduced efficacy.
• Drugs Affecting Phosphate Levels:
• Phosphate binders or supplements may require adjustment.
• P-gp Substrates:
• Erdafitinib is a substrate of P-gp; monitor when used with P-gp inhibitors.
• Food Interactions:
• No significant food interaction reported.
• Alcohol:
• No known direct interaction; however, caution is advised due to hepatic metabolism.

• FDA Approval Expansion (2023):
  Erdafitinib's label was updated to include companion diagnostic test information for identifying FGFR alterations.
• NCCN Guidelines (2024):
  Erdafitinib listed as a preferred second-line treatment option for FGFR-altered metastatic urothelial carcinoma.
• Ongoing Clinical Trials (as of 2025):
  Investigating erdafitinib in combination with immune checkpoint inhibitors (e.g., pembrolizumab) and other solid tumors with FGFR alterations.

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Excursions permitted to 15°C–30°C (59°F–86°F)
• Humidity & Light: Protect from moisture and light. Keep in original container.
• Handling Precautions:
• Keep tablets dry.
• Do not crush or split tablets.
• Reconstitution: Not applicable (oral tablet formulation).